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1.
PeerJ ; 12: e17374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756445

RESUMO

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.


Assuntos
Doença Celíaca , Dieta Livre de Glúten , Interleucina-17 , Interleucina-18 , Periodontite , Saliva , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-17/análise , Masculino , Feminino , Interleucina-18/sangue , Interleucina-18/análise , Interleucina-18/metabolismo , Saliva/química , Saliva/imunologia , Adulto , Periodontite/imunologia , Periodontite/metabolismo , Periodontite/sangue , Interleucina-1beta/sangue , Interleucina-1beta/análise , Interleucina-1beta/metabolismo , Estudos de Casos e Controles , Pessoa de Meia-Idade , Biomarcadores/sangue , Biomarcadores/análise , Adulto Jovem
2.
J Med Virol ; 96(5): e29643, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695269

RESUMO

Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.


Assuntos
Inflamassomos , Piroptose , Piroptose/efeitos dos fármacos , Humanos , Animais , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Interleucina-18/metabolismo , Interleucina-18/genética , SARS-CoV-2 , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia
3.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 284-289, 2024 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-38716601

RESUMO

Objective: To analyze the level and clinical significance of IL-18 and IL-18-binding protein (BP) in the bone marrow of patients with myelodysplastic syndrome (MDS) . Methods: A total of 43 newly diagnosed patients with MDS who were admitted to the Department of Hematology, Tianjin Medical University General Hospital, from July 2020 to February 2021 were randomly selected. The control group consisted of 14 patients with acute myeloid leukemia (AML) and 25 patients with iron-deficiency anemia (IDA). The levels of IL-18 and IL-18 BP in the bone marrow supernatant were measured, and their correlations with MDS severity, as well as the functionality of CD8(+) T cells and natural killer cells, was analyzed. Results: The levels of IL-18, IL-18 BP, and free IL-18 (fIL-18) in the bone marrow supernatant of patients with MDS were higher than in the IDA group. The level of fIL-18 was linearly and negatively correlated with the MDS-International Prognostic Scoring System (IPSS) score. IL-18 receptor (IL-18Rα) expression on CD8(+) T cells in the MDS group was lower than in the IDA group, and the levels of fIL-18 and IL-18Rα were positively correlated with CD8(+) T-cell function in the MDS group. Conclusion: IL-18 BP antagonizes IL-18, leading to a decrease in fIL-18 in the bone marrow microenvironment of patients with MDS, affecting CD8(+) T-cell function, which is closely related to MDS severity; therefore, it may become a new target for MDS treatment.


Assuntos
Medula Óssea , Peptídeos e Proteínas de Sinalização Intercelular , Interleucina-18 , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/metabolismo , Interleucina-18/metabolismo , Medula Óssea/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Masculino , Feminino , Células Matadoras Naturais/metabolismo , Pessoa de Meia-Idade , Relevância Clínica
4.
Sci Rep ; 14(1): 10178, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702410

RESUMO

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1ß and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1ß in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.


Assuntos
Índice de Massa Corporal , Concussão Encefálica , Inflamassomos , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Obesidade , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Feminino , Obesidade/complicações , Inflamassomos/metabolismo , Adulto , Pessoa de Meia-Idade , Concussão Encefálica/complicações , Concussão Encefálica/sangue , Interleucina-18/sangue , Interleucina-18/metabolismo , Estudos Prospectivos , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Caspase 1/metabolismo
5.
BMC Mol Cell Biol ; 25(1): 16, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750444

RESUMO

BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.


Assuntos
Caspase 1 , Doxorrubicina , Oxidases Duais , Insuficiência Cardíaca , Estresse Oxidativo , Piroptose , Espécies Reativas de Oxigênio , Regulação para Cima , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Oxidases Duais/metabolismo , Oxidases Duais/genética , Espécies Reativas de Oxigênio/metabolismo , Humanos , Doxorrubicina/farmacologia , Caspase 1/metabolismo , Linhagem Celular , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo
6.
Zhonghua Gan Zang Bing Za Zhi ; 32(4): 354-362, 2024 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-38733191

RESUMO

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1ß content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1ß, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1ß and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1ß, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1ß, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.


Assuntos
Insuficiência Hepática Crônica Agudizada , Medicamentos de Ervas Chinesas , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Insuficiência Hepática Crônica Agudizada/etiologia , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Masculino , Interleucina-18/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Interleucina-1beta/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas de Transporte/metabolismo
7.
Arch Dermatol Res ; 316(5): 156, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734816

RESUMO

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Caspase 1 , Dermatite Atópica , Inflamassomos , Interleucina-18 , Interleucina-1beta , Peptídeos e Proteínas de Sinalização Intracelular , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas de Ligação a Fosfato , Humanos , Inflamassomos/metabolismo , Inflamassomos/imunologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Macrófagos/metabolismo , Macrófagos/imunologia , Interleucina-1beta/metabolismo , Masculino , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Adulto , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Caspase 1/metabolismo , Pele/patologia , Pele/imunologia , Pele/metabolismo , Índice de Gravidade de Doença , Pessoa de Meia-Idade , Antígenos de Diferenciação Mielomonocítica/metabolismo , Adulto Jovem , Proteínas Reguladoras de Apoptose/metabolismo , Antígenos CD/metabolismo , Proteínas NLR/metabolismo , Estudos de Casos e Controles , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Gasderminas , Molécula CD68 , Proteínas de Ligação a DNA
8.
Nat Commun ; 15(1): 3937, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729924

RESUMO

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.


Assuntos
Apoptose , Criopreservação , Granzimas , Interleucina-15 , Interleucina-18 , Células Matadoras Naturais , Granzimas/metabolismo , Interleucina-15/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Humanos , Interleucina-18/metabolismo , Animais , Criopreservação/métodos , Camundongos , Linhagem Celular Tumoral , Sistemas CRISPR-Cas
9.
Nat Commun ; 15(1): 3933, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730243

RESUMO

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.


Assuntos
Interleucina-18 , Proteínas de Membrana , Receptores de Antígenos Quiméricos , Animais , Interleucina-18/metabolismo , Proteínas de Membrana/agonistas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Humanos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Imunoterapia Adotiva/métodos , Feminino , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico
10.
Nat Commun ; 15(1): 4227, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762592

RESUMO

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vß21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vß21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vß21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.


Assuntos
COVID-19 , Interleucina-18 , Células Matadoras Naturais , Monócitos , Transdução de Sinais , Síndrome de Resposta Inflamatória Sistêmica , Receptor fas , Humanos , Interleucina-18/metabolismo , Criança , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptor fas/metabolismo , Receptor fas/genética , Monócitos/imunologia , Monócitos/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , COVID-19/imunologia , COVID-19/virologia , COVID-19/metabolismo , COVID-19/complicações , Inflamassomos/metabolismo , Inflamassomos/imunologia , SARS-CoV-2/imunologia , Adolescente , Masculino , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Feminino , Pré-Escolar , Análise de Célula Única , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD28/metabolismo , Ativação Linfocitária/imunologia , Receptores de Interleucina-18/metabolismo , Receptores de Interleucina-18/genética , Receptores de Interleucina-18/imunologia
11.
Sci Rep ; 14(1): 7683, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561502

RESUMO

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Neoplasias Gástricas , Humanos , Citocinas/metabolismo , Helicobacter pylori/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Helicobacter/metabolismo , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Gastrite/patologia , Interleucina-12/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Mucosa Gástrica/metabolismo
12.
Cell Death Dis ; 15(4): 244, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575607

RESUMO

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.


Assuntos
Interleucina-18 , Neoplasias Pancreáticas , Humanos , Glicosilação , Interleucina-18/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas/metabolismo , Vias Biossintéticas , Hexosaminas , Microambiente Tumoral , Proteína 1 de Ligação a Y-Box/metabolismo , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética
13.
BMC Pulm Med ; 24(1): 207, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671448

RESUMO

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.


Assuntos
Gasderminas , Pulmão , Piroptose , Quinuclidinas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Quinuclidinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo
14.
Neuroreport ; 35(9): 558-567, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38687900

RESUMO

Heat stroke induced cerebral damage via neuroinflammation. This study aimed to approach whether heat stress would promote NOD-like receptor protein 3 (NLRP3) inflammasome via reactive oxygen species (ROS). The mice were randomly divided into the sham group, the heat stress group, and the heat stress + TEMPOL (ROS scavenger) group. And the NLRP3 -/- mice were applied and divided into the NLRP3 -/-  + sham group and the NLRP3 -/-  + heat stress group. Furthermore, the BV2 cells were divided into four groups following the intervention measures: the heat stress + TEMPOL group, the heat stress + Z-VAD-FMK (caspase-1 inhibitor) group, the heat stress group, and the control group. ROS levels were examined. The expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 were detected by western blotting and double immunofluorescence. We found that heat stress attack induced excessive ROS in microglia and subsequently activated NLRP3 inflammasome in both mice and BV2 cells. When ROS scavenged, the expression level of NLRP3 was downregulated. Furthermore, with NLRP3 inflammasome activation, the expression levels of caspase-1, IL-1ß, and IL-18 were increased. In NLRP3 -/- mice, however, the caspase-1, IL-1ß, and IL-18 were significantly declined. Further experiments showed that pretreatment of caspase-1 inhibitor decreased the expression levels of IL-1ß and IL-18. These results suggest that heat stress attack caused neuroinflammation via excessive ROS activating the NLRP3 inflammasome in microglia cells.


Assuntos
Golpe de Calor , Inflamassomos , Interleucina-18 , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Interleucina-18/metabolismo , Camundongos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Golpe de Calor/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Camundongos Knockout , Masculino , Caspase 1/metabolismo , Resposta ao Choque Térmico/fisiologia , Resposta ao Choque Térmico/efeitos dos fármacos
15.
Immun Inflamm Dis ; 12(4): e1241, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38629728

RESUMO

BACKGROUND: Inflammation in adipose tissue, resulting from imbalanced caloric intake and energy expenditure, contributes to the metabolic dysregulation observed in obesity. The production of inflammatory cytokines, such as IL-1ß and IL-18, plays a key role in this process. While IL-1ß promotes insulin resistance and diabetes, IL-18 regulates energy expenditure and food intake. Previous studies have suggested that caspase-1, activated by the Nlrp3 inflammasome in response to lipid excess, mediates IL-1ß production, whereas activated by the Nlrp1b inflammasome in response to energy excess, mediates IL-18 production. However, this has not been formally tested. METHODS: Wild-type and caspase-1-deficient Balb/c mice, carrying the Nlrp1b1 allele, were fed with regular chow or a high-fat diet for twelve weeks. Food intake and mass gain were recorded weekly. At the end of the twelve weeks, glucose tolerance and insulin resistance were evaluated. Mature IL-18 protein levels and the inflammatory process in the adipose tissue were determined. Fasting lipid and cytokine levels were quantified in the sera of the different experimental groups. RESULTS: We found that IL-18 production in adipose tissue is independent of caspase-1 activity, regardless of the metabolic state, while Nlrp3-mediated IL-1ß production remains caspase-1 dependent. Additionally, caspase-1 null Balb/c mice did not develop metabolic abnormalities in response to energy excess from the high-fat diet. CONCLUSION: Our findings suggest that IL-18 production in the adipose tissue is independent of Nlrp3 inflammasome and caspase-1 activation, regardless of caloric food intake. In contrast, Nlrp3-mediated IL-1ß production is caspase-1 dependent. These results provide new insights into the mechanisms underlying cytokine production in the adipose tissue during both homeostatic conditions and metabolic stress, highlighting the distinct roles of caspase-1 and the Nlrp inflammasomes in regulating inflammatory responses.


Assuntos
Tecido Adiposo , Caspase 1 , Caspases Iniciadoras , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Tecido Adiposo/metabolismo , Caspase 1/metabolismo , Caspases/metabolismo , Citocinas/metabolismo , Inflamassomos/metabolismo , Resistência à Insulina , Interleucina-18/metabolismo , Lipídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspases Iniciadoras/metabolismo
16.
J Ethnopharmacol ; 328: 117956, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428658

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration. AIM OF THE STUDY: This study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17 cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice. MATERIALS AND METHODS: 61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.96 and 11.83 g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1ß, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-Iß, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome. RESULTS: GQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17 cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1ß, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1ß. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function. CONCLUSIONS: GQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17 cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.


Assuntos
Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Th17 , Ocludina/metabolismo , RNA Ribossômico 16S/metabolismo , Camundongos Endogâmicos CBA , Colite/tratamento farmacológico , Citocinas/metabolismo , Trinitrobenzenos/metabolismo , Trinitrobenzenos/farmacologia , Trinitrobenzenos/uso terapêutico , Anti-Inflamatórios/farmacologia , Peso Corporal , Caspases/metabolismo , Modelos Animais de Doenças , Colo
17.
Cytokine ; 177: 156565, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442443

RESUMO

BACKGROUND: Perinatal hypoxia triggers the release of cytokines and chemokines by neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, producing proinflammatory molecules. The brain damage extension seems to be related to both the severity of hypoxia and the balance between pro and anti-inflammatory response and can be explored with neuroimaging. AIMS: The aim of this preliminary study was to explore possible relationships between plasma levels of inflammatory cytokines/chemokines and the severe brain damage detectable by Magnetic Resonance Imaging (MRI), performed during the hospitalization. METHODS: In 10 full terms neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), divided into cases and controls, according to MRI results, we measured and compared the plasma levels of CCL2/MCP-1, CXCL8, GFAP, IFN y, IL-10, IL-18, IL-6, CCL3, ENOLASE2, GM-CSF, IL-1b, IL-12p70, IL-33, TNFα, collected at four different time points during TH (24, 25-48, 49-72 h of life, and 7-10 days from birth). Five of enrolled babies had pathological brain MRI (cases) and 5 had a normal MRI examination (controls). Cytokines were measured by Magnetic Luminex Assay. MRI images were classified according to Barkovich's score. RESULTS: Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. At T4, levels tended to get closer again (except for IL-6, IL10 and IL18). Infants with worse MRI showed higher plasmatic GFAP levels than those with normal MRI, while their IL-18 was lower. The mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both groups. CONCLUSION: In a small number of infants with worse brain MRI, we found higher levels of GFAP and of IL-10 at T4 and a trend toward low IL-18 levels than in infants with normal MRI, considered early biomarker of brain damage and a predictor of adverse outcome, respectively. The greatest, although not significant, difference between the levels of molecules was found in cases and controls at time points T2 and T3, during TH.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Recém-Nascido , Lactente , Feminino , Gravidez , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Citocinas/metabolismo , Interleucina-10/metabolismo , Interleucina-18/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Interleucina-6/metabolismo , Encéfalo/metabolismo , Imageamento por Ressonância Magnética/métodos , Quimiocinas/metabolismo , Neuroimagem
18.
BMC Ophthalmol ; 24(1): 144, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553670

RESUMO

AIM: To elaborate the underlying mechanisms by which IL-1ß promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs). METHODS: 400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1ß mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships. RESULTS: After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1ß was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1ß silencing reversed this effect. In addition, IL-1ß negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1ß silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs. CONCLUSION: Highly expressed IL-1ß promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3.


Assuntos
Síndromes do Olho Seco , MicroRNAs , Humanos , Piroptose , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-33/genética , Regulação para Baixo , Apoptose , Síndromes do Olho Seco/genética , Células Epiteliais/metabolismo , Caspases/genética , Fator de Transcrição STAT3/genética
19.
Cell Biochem Funct ; 42(3): e3997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38555506

RESUMO

Allergic rhinitis (AR) is characterized by nasal symptoms such as rubbing and sneezing, often triggered by allergen exposure. The purpose of this study is to dissect the roles of NLRP3-mediated immune modulation and macrophage pyroptosis in modulating T cell differentiation within the context of ovalbumin (OVA)-induced AR in mice. OVA-induced AR was established in mice, evaluating nasal symptoms, macrophage infiltration, cytokine levels, and T cell differentiation. Manipulations using NLRP3-/-, ASC-/- mice, clodronate liposome treatment, and NLRP3 inhibitor MCC950 were performed to assess their impact on AR symptoms and immune responses. Following OVA stimulation, increased nasal symptoms were observed in the OVA group along with augmented GATA3 expression and elevated IL-4 and IL-1b levels, indicative of Th2 polarization and cellular pyroptosis involvement. NLRP3-/- and ASC-/- mice exhibited reduced CD3+ T cells post OVA induction, implicating cellular pyroptosis in AR. Macrophage depletion led to decreased IgE levels, highlighting their involvement in allergic responses. Further investigations revealed enhanced macrophage pyroptosis, influencing Th1/Th2 differentiation in AR models. IL-18 released through NLRP3-mediated pyroptosis induced Th2 differentiation, distinct from IL-1b. Additionally, MCC950 effectively mitigated AR symptoms by modulating Th2 responses and reducing macrophage infiltration. This comprehensive study unravels the pivotal role of NLRP3-mediated immune modulation and macrophage pyroptosis in Th1/Th2 balance regulation in OVA-induced AR. Targeting NLRP3 pathways with MCC950 emerged as a promising strategy to alleviate AR symptoms, providing insights for potential therapeutic interventions in AR management.


Assuntos
Rinite Alérgica , Células Th2 , Camundongos , Animais , Células Th2/metabolismo , Interleucina-18/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mucosa Nasal/metabolismo , Ovalbumina/metabolismo , Ovalbumina/farmacologia , Rinite Alérgica/tratamento farmacológico , Citocinas/metabolismo , Imunomodulação , Imunidade , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
20.
Bull Exp Biol Med ; 176(4): 423-427, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38488959

RESUMO

In 89 patients with COVID-19, the ratios between IL-18, free IL-18, and IL-18-binding protein (IL-18BP) were analyzed depending on severity and outcome of the disease. At admission to the hospital, the levels of IL-18 and free IL-18 were significantly higher than 3 months after discharge from the hospital, the levels IL-18BP of being almost the same. In patients with more severe lung injury (computed tomography data), the levels of IL-18 and free IL-18 were higher and IL-18BP levels were lower than in patients with mild and moderate COVID-19. Three months after discharge from the hospital, no differences between these parameters were found. In 9 patients who died in the hospital, free IL-18 levels were significantly higher and IL-18BP levels were lower than in survivors. Thus, high levels of bioactive free IL-18 in combination with low levels of IL-18BP can be indicative of severe inflammatory phase of COVID-19 and the risk of worse clinical outcomes.


Assuntos
COVID-19 , Interleucina-18 , Humanos , Interleucina-18/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Transporte , Interleucina-1beta/metabolismo
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