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1.
J Med Virol ; 94(1): 154-160, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427934

RESUMO

In this study, we investigated the role and relationship between the cytokine profile and protective vitamin D by measuring their serum levels in COVID-19 intensive care unit patients with severe illnesses. A total of 74 patients were included in our study. Patients were divided into two groups. Patients in the COVID-19 group (n = 31) and individuals without a history of serious illness or infection were used as the control group (n = 43). The serum concentrations of interleukin-1 (IL-1), IL-6, IL-10, IL-21, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assays. Levels of serum vitamin D were detected with Liquid chromatography-mass spectrometry methodologies. TNF-α, IL-1, IL-6, IL-10, IL-21, and vitamin D levels were measured in all patients. The serum cytokine levels in the COVID-19 patient group were significantly higher (151.59 ± 56.50, 140.37 ± 64.32, 249.02 ± 62.84, 129.04 ± 31.64, and 123.58 ± 24.49, respectively) than control groups. Serum vitamin D was also significantly low (6.82 ± 3.29) in patients in the COVID-19 group than the controls (21.96 ± 5.39). Regarding the correlation of vitamin D with cytokine levels, it was significantly variable. Our study shows that COVID-19 patients are associated with lower serum vitamin D and higher pro-inflammatory cytokines associated with increased virus presence. Our data provide more evidence of the anti-inflammatory effect of vitamin D on COVID-19 patients and the protective effects of vitamin D on risk were demonstrated.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Citocinas/sangue , Vitamina D/sangue , Feminino , Humanos , Inflamação , Interleucina-1/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
2.
PLoS One ; 16(11): e0258743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34758029

RESUMO

BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional adaptive immune cells subsets is not well characterized. We investigated the impact of BCG vaccination on the frequencies of T cell subsets and common gamma c (γc) cytokines in a group of healthy elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrate that BCG vaccination induced enhanced frequencies of central (p<0.0001) and effector memory (p<0.0001) CD4+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001), stem cell memory (p = 0.0001) CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central (p = 0.0008), effector (p<0.0001) and terminal effector memory (p<0.0001) CD8+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001) and stem cell memory (p = 0.0034) CD8+T cells. BCG vaccination also induced enhanced plasma levels of IL-7 (p<0.0001) and IL-15 (p = 0.0020) but diminished levels of IL-2 (p = 0.0033) and IL-21 (p = 0.0020). Thus, BCG vaccination was associated with enhanced memory T cell subsets as well as memory enhancing γc cytokines in elderly individuals, suggesting its ability to induce non-specific adaptive immune responses.


Assuntos
Vacina BCG/imunologia , Citocinas/imunologia , Memória Imunológica/imunologia , Subunidade gama Comum de Receptores de Interleucina/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Feminino , Humanos , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Vacinação/métodos
3.
Aging (Albany NY) ; 13(21): 23895-23912, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725309

RESUMO

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1ß, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.


Assuntos
COVID-19 , Estado Terminal , Interleucinas/sangue , Pneumonia Viral , Fator de Necrose Tumoral alfa/sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/terapia , China/epidemiologia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Testes Imunológicos/métodos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Valor Preditivo dos Testes , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Inibidores do Fator de Necrose Tumoral/uso terapêutico
4.
J Interferon Cytokine Res ; 41(11): 407-414, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34788130

RESUMO

Genetic polymorphisms at the IFNL4 loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the IFNL4 genotype and hepatitis C virus clearance. However, an influence of the IFNL4 genotype on the adaptive immune system was suggested by several studies but never investigated in humans. In this cross-sectional study, we have genotyped 201 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive participants for 3 IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) and stratified them according to the IFNλ4 activity. Based on this stratification, we investigated the association between the IFNL4 genotype and the antibody as well as the CD8+ T cell response in the acute phase of the SARS-CoV-2 infection. We observed no differences in the genotype distribution compared with a Danish reference cohort or the 1,000 Genome Project, and we were not able to link the IFNL4 genotype to changes in either the antibody or CD8+ T cell responses of these patients.


Assuntos
Imunidade Adaptativa/imunologia , COVID-19/imunologia , Interleucinas/imunologia , SARS-CoV-2/imunologia , Imunidade Adaptativa/genética , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Estudos Transversais , Feminino , Genótipo , Humanos , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Polimorfismo de Nucleotídeo Único/imunologia , SARS-CoV-2/genética , Adulto Jovem
5.
Vet Dermatol ; 32(6): 631-e169, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34796564

RESUMO

BACKGROUND: To optimise the interleukin (IL)-31-blocking therapy in atopic dermatitis (AD), an understanding of the chronology in the expression of IL-31 and its receptor (IL-31RA) is needed. HYPOTHESIS/OBJECTIVES: (i) To assess the chronological expression of IL-31 in canine AD skin lesions, (ii) to compare it with serum IL-31 levels and macroscopic skin lesion scores, and (iii) to determine the identity of IL-31- and IL-31RA-positive cells. ANIMALS: Four atopic dogs sensitised to house dust mites. METHODS AND MATERIALS: Skin and blood samples were obtained 0 h, 24 h, 48 and 96 h after allergen provocation. IL-31 and IL-31RA single-staining immunofluorescence (IF), as well as IL-31/CD3, IL-31/CD4 and IL-31RA/ß3-tubulin double-staining IF were performed. The IL-31-positive cells were counted subjectively. RESULTS: The peak IL-31 expression for three of four dogs occurred 24 h or 48 h postchallenge; it started to decrease at 96 h. There was no significant correlation between the IL-31 expression scores and the serum IL-31 concentrations or the macroscopic skin lesion scores (P = 0.35 and P = 0.36, respectively). The majority of IL-31-positive cells were positive for CD3 (range 91-100%) and CD4 (range 63-100%), indicating that they were helper T (Th) cells. Unexpectedly, sebaceous glands were strongly immunolabelled with IL-31; the extinction of this positivity after immunoabsorption with IL-31 further supported the validity of this immunostaining. The IL-31RA was visualised on keratinocytes and a small proportion of dermal nerves. CONCLUSIONS AND CLINICAL IMPORTANCE: The early and transient production of IL-31 by Th cells supports the concept of using IL-31 inhibiting strategies as a proactive therapy to prevent flares of AD skin lesions.


Assuntos
Dermatite Atópica , Doenças do Cão , Animais , Dermatite Atópica/veterinária , Cães , Interleucinas , Queratinócitos , Pele
7.
Biomater Sci ; 9(22): 7402-7411, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34709241

RESUMO

Interleukin (IL)-22 is a multifunctional cytokine with a very short half-life that activates STAT3 and can elicit strong anti-inflammatory effects in the intestine but can induce inflammation in other sites. Several long-circulating IL-22 fusion proteins have been manufactured to date; however, those were associated with adverse effects in other organs limiting their utility for treating intestinal inflammation. Targeted delivery of IL-22 to the intestine could utilize its anti-inflammatory properties and overcome systemic toxicity. Therefore, this study aimed to synthesise large pore mesoporous silica nanoparticles (LPMSN), load recombinant (r)IL-22 in the LPMSN and test its bioactivity in the STAT3 reporter LS174T, wild type LS174T, Caco-2 intestinal epithelial cells, and healthy human colonic organoids. Our data showed one hundred percent loading capacity (w/w) of the synthesised LPMSN, which prolonged IL-22 induced STAT3 luciferase activities in LS174T and p-STAT3 immunofluorescence in Caco-2 cells. LPMSN also stabilized and increased the permeability of rIL-22 across Caco-2 monolayers. Moreover, LPMSN-IL-22 retained the functionality of the cytokine in human colonic organoids. Taken together, these data demonstrate the protection and effective delivery of IL-22 using bio-nanomaterials (LPMSN) that could enable targeted oral delivery of this IL-22.


Assuntos
Dendrímeros , Nanopartículas , Células CACO-2 , Humanos , Interleucinas , Dióxido de Silício
8.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638962

RESUMO

Gaining detailed knowledge about sex-related immunoregulation remains a crucial prerequisite for the development of adequate disease models and therapeutic strategies enabling personalized medicine. Here, the key parameter of the production of cytokines mediating disease resolution was investigated. Among these cytokines, STAT3-activating interleukin (IL)-22 is principally associated with recovery from tissue injury. By investigating paradigmatic acetaminophen-induced liver injury, we demonstrated that IL-22 expression is enhanced in female mice. Increased female IL-22 was confirmed at a cellular level using murine splenocytes stimulated by lipopolysaccharide or αCD3/CD28 to model innate or adaptive immunoactivation. Interestingly, testosterone or dihydrotestosterone reduced IL-22 production by female but not by male splenocytes. Mechanistic studies on PMA/PHA-stimulated T-cell-lymphoma EL-4 cells verified the capability of testosterone/dihydrotestosterone to reduce IL-22 production. Moreover, we demonstrated by chromatin immunoprecipitation that testosterone impairs binding of the aryl hydrocarbon receptor to xenobiotic responsive elements within the murine IL-22 promoter. Overall, female mice undergoing acute liver injury and cultured female splenocytes upon inflammatory activation display increased IL-22. This observation is likely related to the immunosuppressive effects of androgens in males. The data presented concur with more pronounced immunological alertness demonstrable in females, which may relate to the sex-specific course of some immunological disorders.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Expressão Gênica/efeitos dos fármacos , Interleucinas/genética , Interleucinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetaminofen/sangue , Imunidade Adaptativa/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Di-Hidrotestosterona/farmacologia , Modelos Animais de Doenças , Feminino , Imunidade Inata/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/imunologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores Sexuais , Baço/citologia , Baço/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Testosterona/farmacologia
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(10): 872-880, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34670663

RESUMO

Objective To compare the effect of different cytokine combinations combined with anti-CD3/CD28 beads in vitro inducing the generation of central memory T cell (Tcm). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors. Naive CD8+ T cells were purified using immunomagnetic beads and stimulated with CD3/CD28 antibody for 48 hours. Cells were treated with different cytokine combinations as follows: Interleukin-2(IL-2), IL-7/IL-15, IL-7/IL-15/IL-21, and IL-7/IL-15/IL-21/IL-23. The automatic blood cell counting instrument was used for cell counting. 5, 6-carboxyfluorescein diacetate succinimidyl ester (CFSE)was employed to test the cell proliferation and flow cytometry was adopted to measure the immune memory phenotype, apoptosis and intracellular factor expression of CD8+ T cells induced by different cytokine combinations. The expression of Bcl-2 was determined by Western blot analysis. Results Unlike other cytokine combinations, IL-7/IL-15/IL-21/IL-23 promoted the proliferation of CD8+ T cells and significantly increased the expression of CD8+CD62L+CD45RA- central memory T cell subsets. At the same time, IL-7/IL-15/IL-21/IL-23 treatment significantly reduced the secretion levels of IFN-γ, perforin, and granzyme B. The level of cell apoptosis was also significantly decreased. Conclusion The cytokines combination of IL-7/IL-15/IL-21/IL-23 can effectively induce the differentiation of naive CD8+T cells to CD8+ Tcm cells in vitro, which provides a new strategy for the generation of human CD8+ Tcm in immunotherapy.


Assuntos
Memória Imunológica , Interleucina-7 , Linfócitos T CD8-Positivos , Humanos , Interleucina-15 , Interleucina-23 , Interleucinas , Leucócitos Mononucleares
10.
Rev Alerg Mex ; 68(3): 180-184, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34634848

RESUMO

OBJECTIVES: The primary objective of this study was to define the relationship between vitamin D levels and interleukins (IL) 1ß and 6 as inflammatory markers in a healthy population. As a secondary objective, to measure the prevalence of insufficiency/ deficiency of vitamin D in the same population. METHODS: A sample of 43 healthy blood donors, without chronic-degenerative, inflammatory, or infectious diseases, and without obesity, was selected. Serum levels of IL-1ß and IL-6 were measured in individuals with insufficiency or deficiency of vitamin D. The correlation between vitamin D and interleukins was measured using Spearman's rho. RESULTS: No correlation was found between levels of vitamin D and interleukins. In addition, a prevalence of insufficiency/deficiency of vitamin D was found in 95.3% of the sample. CONCLUSIONS: In healthy subjects with deficiency or insufficiency of vitamin D, there is no association between the levels of this vitamin and IL-1ß and IL-6.


Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Interleucina-1beta , Interleucinas , Deficiência de Vitamina D/epidemiologia , Vitaminas
11.
J Int Med Res ; 49(10): 3000605211053233, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34704484

RESUMO

OBJECTIVE: This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. METHODS: Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. RESULTS: Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83-0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78-0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71-0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78-0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78-0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68-0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68-0.92), but not in Africans or Americans. CONCLUSION: This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans.INPLASY registration number: INPLASY202170056.


Assuntos
Artrite Reumatoide , Interleucina-17 , Artrite Reumatoide/genética , Predisposição Genética para Doença , Humanos , Interleucina-17/genética , Interleucinas , Polimorfismo de Nucleotídeo Único/genética
12.
Sci Rep ; 11(1): 21185, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34707167

RESUMO

Interferon lambda 4 (IFNλ4) has shown antiviral activity against RNA viruses, including some coronaviruses. Besides, genetic variants of IFNL4 can be predictive of the clearance of RNA viruses. However, little is known about the effect of these genetic variants on SARS-CoV-2 infection. In this study, we investigated whether there was a relationship of the rs12979860 polymorphism of IFNL4 with COVID-19. We found that the T allele of rs12979860 was overexpressed in COVID-19 patients with regard to the general population without this disease (36.16% vs. 26.40%, p = 6.4 × 10-4; OR 0.633 C vs T; 95% CI 0.487, 0.824), suggesting that this allele could be a risk factor for COVID-19. Accordingly, the CC genotype was significantly lower in COVID-19 patients compared to controls (37.85% vs. 55.51%, p = 8 × 10-5; OR 0.488; 95% CI 0.342, 0.698). These results were not affected by sex, age, and disease severity in patients with COVID-19. Our findings suggest that, like other infectious diseases caused by RNA viruses, genetic variants of IFNL4 can predispose to COVID-19. Confirmation of our results may contribute to better understanding the mechanisms of this disease.


Assuntos
COVID-19/genética , COVID-19/imunologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Espanha/epidemiologia
13.
PLoS One ; 16(10): e0254985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34597299

RESUMO

BACKGROUND: The goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS). SUMMARY BACKGROUND DATA: No therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22. STUDY DESIGN: ARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4. RESULTS: In the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham. CONCLUSIONS: IL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.


Assuntos
Fragmentos Fc das Imunoglobulinas/farmacologia , Interleucinas/farmacologia , Lesão Pulmonar/tratamento farmacológico , Pneumonia/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/patologia , Contagem de Linfócitos , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia/patologia , Receptores de Interleucina/metabolismo , Proteínas Recombinantes/farmacologia , Síndrome do Desconforto Respiratório/patologia , Mucosa Respiratória/patologia
14.
PLoS One ; 16(10): e0255309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618816

RESUMO

BACKGROUND: Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown. METHODS: Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection. RESULTS: Surprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not. CONCLUSIONS: These data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense.


Assuntos
Interferons/análise , Interferons/imunologia , Interleucinas/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Linhagem Celular , Coinfecção/imunologia , Coinfecção/microbiologia , Cães , Feminino , Interferons/genética , Interleucinas/genética , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/patologia , Polimorfismo Genético/genética , Infecções Estafilocócicas/prevenção & controle , Superinfecção/imunologia , Superinfecção/microbiologia , Carga Viral/imunologia
15.
Nat Commun ; 12(1): 5947, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642338

RESUMO

Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.


Assuntos
Fibroblastos/imunologia , Interleucinas/genética , Receptores de Interleucina/genética , Escleroderma Sistêmico/imunologia , Células Th2/imunologia , Adulto , Idoso , Animais , Anticorpos Monoclonais/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/imunologia , Modelos Animais de Doenças , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica , Humanos , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucinas/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Receptores de Interleucina/antagonistas & inibidores , Receptores de Interleucina/imunologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th2/efeitos dos fármacos , Células Th2/patologia
16.
Nihon Yakurigaku Zasshi ; 156(5): 288-291, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34470933

RESUMO

Interleukin-19 (IL-19) is a member of the IL-10 family and is an anti-inflammatory cytokine produced mainly by macrophages, epithelial cells, and vascular smooth muscle cells. In addition, receptors for IL-19, IL-20 receptor 1 and IL-20 receptor 2, are also expressed in the cells mentioned above. The last 10 years from the finding of IL-19, investigations underline the anti-inflammatory role of IL-19 in the human diseases such as psoriasis, asthma, arteriosclerosis, and inflammatory bowel disease. If it is a pro-inflammatory cytokine, therapeutic applications may include the use of neutralizing antibodies, however, because IL-19 exhibits anti-inflammatory effects, recombinant products may be useful in therapeutic applications. However, the therapeutic applications of IL-19 for human disease have not yet been developed. In this review, we present the new findings on the preventive and therapeutic effects of IL-19 on various mouse disease models. Increasing knowledge about mouse disease models will increase the feasibility of future human disease applications.


Assuntos
Doenças Inflamatórias Intestinais , Psoríase , Animais , Anti-Inflamatórios/farmacologia , Citocinas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucinas , Camundongos
17.
PLoS One ; 16(9): e0257185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516566

RESUMO

PURPOSE: Tuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized. METHODS: In this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10. RESULTS: In freshly isolated PBMCs, percentages of CD3-CD56+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3-CD56+CD16+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32α, IL-15 and IFN-γ in response to Mtb antigens in LTBI+ individuals. CONCLUSION: We studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-γ and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/imunologia , Memória Imunológica , Células Matadoras Naturais/imunologia , Tuberculose Latente/complicações , Tuberculose Latente/imunologia , Adulto , Comunicação Celular , Proliferação de Células , Quimiocinas/biossíntese , Granzimas/biossíntese , Infecções por HIV/patologia , Humanos , Interferon gama/metabolismo , Interleucina-15/biossíntese , Interleucinas/metabolismo , Tuberculose Latente/patologia , Subpopulações de Linfócitos/imunologia , Monócitos/metabolismo
18.
Exp Cell Res ; 407(2): 112784, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34508746

RESUMO

Inflammation is an essential factor contributing to sepsis-induced endothelial cell (EC) activation. Interleukin-35 (IL-35) is an anti-inflammatory/immunosuppressive cytokine that exerts protective effects on many inflammatory diseases. In this study, we investigated the effects of IL-35 on lipopolysaccharide (LPS)-induced EC activation and the potential underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (1 µg/ml) for 24 h and then cocultured with different concentrations (0, 1, 10, or 100 ng/ml) of recombinant human IL-35 (rhIL-35) for 12 h. Flow cytometry analysis revealed that IL-35 inhibited LPS-induced HUVEC apoptosis in a dose-dependent manner. RT-qPCR and Western blot analyses showed significantly higher mRNA and protein levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the inflammatory factors IL-6 and IL-8 in the LPS group than in the control group. These changes were alleviated by IL-35 treatment, suggesting that IL-35 protects ECs by downregulating inflammation. Furthermore, IL-35 induced signal transducer and activator of transcription 1 (STAT1) and STAT4 activation and promoted their interaction. Blocking STAT1 or STAT4 expression by fludarabine (STAT1 inhibitor) treatment or siRNA-STAT4-interfering fragment transfection inhibited the protective effect of IL-35 on ECs. Moreover, we observed a similar protective effect of IL-35 treatment on ECs in a mouse sepsis model induced by intraperitoneal LPS injection. This study indicated that IL-35 exerts anti-inflammatory and antiapoptotic effects on LPS-induced EC activation by activating the STAT1 and STAT4 signaling pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose , Endotélio Vascular/metabolismo , Inflamação/prevenção & controle , Interleucinas/metabolismo , Lipopolissacarídeos/toxicidade , Sepse/prevenção & controle , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Regulação da Expressão Gênica , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/administração & dosagem , Interleucinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/metabolismo , Sepse/induzido quimicamente , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais
19.
Acta Derm Venereol ; 101(9): adv00558, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34515804

RESUMO

Current understanding of the underlying pathophysiology of hidradenitis suppurativa (HS) links the disease with proinflammatory activation and autoimmune processes. This study investigated serum levels of interleukin (IL)-22, a cytokine critically involved in epithelial homeostasis, in the context of the broad clinical spectrum of patients with HS. The study also assessed the relationship between serum IL-22 and pro-inflammatory activation (as evidenced by serum level of IL-6) and serum hepcidin (central regulator of systemic iron homeostasis). Serum concentrations of IL-22 were assessed in 74 patients with HS and 15 healthy subjects. Compared with healthy controls, patients with HS demonstrated decreased levels of serum IL-22 (median; interquartile range (IQR): 12.4 pg/ml (9.8; 23.5) vs 34.8 pg/ml (24.8; 39.8), p < 0.001 vs controls). Disease severity (assessed both with Hurley staging and Hidradenitis Suppurativa Severity Index) did not differentiate IL-22 levels (p > 0.1 in both comparisons). Serum levels of IL-22 and IL-6 did not correlate with each other (R=-0.17, p = ns). In a subgroup of 24 patients with HS with pro-inflammatory activation, the mean level of IL-22 was similar to that of the remaining patients (median (IQR): 9.8 pg/ml (8.5; 15.0) vs 12.0 pg/ml (9.4; 16.3), p = ns). Patients with HS demonstrated a decreased level of hepcidin (mean: 31.3 ± 25.9 pg/ml), which correlated with the levels of IL-22 (R=0.36, p <0.05). Patients with HS demonstrated significantly decreased levels of serum IL-22, which was neither correlated with pro-inflammatory status nor associated with disease severity, but correlated modestly with serum hepcidin.


Assuntos
Hidradenite Supurativa , Citocinas , Hepcidinas , Hidradenite Supurativa/diagnóstico , Humanos , Interleucinas
20.
Clin Lab ; 67(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542965

RESUMO

BACKGROUND: Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. METHODS: This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. RESULTS: Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). CONCLUSIONS: The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women.


Assuntos
Interleucina-27 , Pré-Eclâmpsia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-27/genética , Interleucinas , Irã (Geográfico)/epidemiologia , Placenta , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Gravidez
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