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1.
Anim Sci J ; 91(1): e13473, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33078508

RESUMO

Dairy cows often suffer metabolic disorders due to the challenges of the transition period. The aim of study was to determine the effects of feeding pomegranate by-product silage (PBS) on feed intake and some blood parameters, such as non-esterified fatty acids (NEFA) and beta hydroxy butyric acid (BHBA), interleukin-1 (IL-1), serum amyloid-A (SAA), prostaglandin F2α metabolites (PGFM), and progesterone (P4) in fresh Holstein cows. The experimental groups were as follows: CON (0 g PBS of DM) and PBS (120 g PBS of DM). Results showed that replacing corn silage with PBS had no effect on dry matter intake (DMI) throughout the study. The CON group had highest (p < .05) NEFA at 14 d postpartum and serum BHBA was decreased by feeding PBS, especially on days 21 (p < .05) and 28 (p < .05) and the entire study (p < .01). Cows fed PBS had lower (p < .05) serum Malondialdehyde (MDA) than CON cows at different times. Feeding PBS decreased (p < .01) serum IL-1 compared to CON group (216.7 versus. 515.5 Pg/ml) at 28 d postpartum, and also cows fed 120 g PBS had higher (p < .01) serum P4. It was concluded that feeding PBS had no adverse effect on feed intake, milk production, and some reproductive parameters. Moreover, PBS positively affected serum metabolites in fresh dairy cows.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Bovinos/metabolismo , Bovinos/fisiologia , Indústria de Laticínios , Dieta/veterinária , Dinoprosta/metabolismo , Ingestão de Alimentos , Romã (Fruta) , Silagem , Ácido 3-Hidroxibutírico/sangue , Animais , Ácidos Graxos não Esterificados/sangue , Feminino , Inflamação , Interleucina-1/sangue , Lactação , Malondialdeído/sangue , Reprodução
2.
PLoS One ; 15(9): e0239295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941525

RESUMO

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer, particularly in ulcerative colitis (UC) when the majority of colon epithelial cells may be exposed to inflammation-associated mutagenesis. In addition to mutagenesis generated by oxidative stress, inflammation can induce activation-induced cytidine deaminase (Aicda), a mutator enzyme in the APOBEC family, within colon epithelial cells. This study tested the hypothesis that deletion of the Aicda gene could protect against the development of inflammation-associated colorectal cancers, using a model of UC-like colitis in "T/I" mice deficient in TNF and IL10. Results showed that T/I mice that were additionally Aicda-deficient ("TIA" mice) spontaneously developed moderate to severe UC-like colitis soon after weaning, with histologic features and colon inflammation severity scores similar those in T/I mice. Although the mean survival of TIA mice was decreased compared to T/I mice, multivariable analysis that adjusted for age when neoplasia was ascertained showed a decreased numbers of neoplastic colorectal lesions in TIA mice, with a trend toward decreased incidence of neoplasia. Aicda deficiency increased serum IL1α and slightly decreased IL12p40 and M-CSF, as compared with T/I mice, and led to undetectable levels of IgA, IgG1, IgG2a, IgG2b, and IgG3. Taken together, these studies show that Aicda deficiency can decrease the number of neoplastic lesions but is not sufficient to prevent the risk of inflammation-associated colorectal neoplasia in the setting of severe UC-like inflammation. The TIA model may also be useful for assessing the roles of antibody class-switch recombination deficiency and somatic hypermutation on regulation of microbiota and inflammation in the small intestine and colon, as well as the pathogenesis of colitis associated with hyper-IgM syndrome in humans. Further studies will be required to determine the mechanisms that drive early mortality in TIA mice.


Assuntos
Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Citidina Desaminase/genética , Animais , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/etiologia , Citidina Desaminase/deficiência , Feminino , Deleção de Genes , Imunoglobulinas/sangue , Interleucina-1/sangue , Interleucina-10/genética , Interleucina-12/sangue , Fator Estimulador de Colônias de Macrófagos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética
3.
BMC Neurol ; 20(1): 307, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814555

RESUMO

BACKGROUND: Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS: We evaluated the serum levels of IL-36 (IL-36α, IL-36ß and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS: Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS: The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.


Assuntos
Biomarcadores/sangue , Interleucina-1/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
4.
Trials ; 21(1): 468, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: covidwho-506033

RESUMO

OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4th 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bélgica , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Interações Hospedeiro-Patógeno , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Interleucina-1/antagonistas & inibidores , Interleucina-1/sangue , Interleucina-1/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Interleucina-6/imunologia , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/sangue , Receptores de Interleucina-6/imunologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
5.
Clin Exp Hypertens ; 42(7): 669-674, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32476486

RESUMO

AIM: Preeclampsia is one of the major causes of perinatal, fetal, and maternal mortality and morbidity. The aim of this study was to investigate the association of serum interleukin 37 (IL 37) with preeclampsia. METHODS: 39 women with preeclampsia were included as the study group. 38 healthy, and normotensive pregnant women, at similar gestational week with similar gravidity volunteered as the control group. Clinical findings, biochemical parameters, maternal and perinatal outcomes, and the serum concentrations of IL37 were compared between the groups. The relationship of IL 37 concentrations with clinical findings and blood pressure outcomes were also investigated. RESULTS: Maternal serum IL 37 concentrations were significantly higher in patients with preeclampsia compared to the healthy pregnant women in the control group (p = .005). IL 37 positively correlated systolic blood pressure (BP) (r = 0.344, p = .002), and diastolic BP (r = 0.332, p = .003). IL 37 was identified as an independent predictor of preeclampsia. CONCLUSIONS: Serum IL 37 concentrations were higher in preeclamptic patients compared to healthy pregnant women. Furthermore, IL 37 concentrations achieved success in identifying preeclampsia with hypertension. Increased IL 37 activity may have a role in the pathophysiology of preeclampsia.


Assuntos
Pressão Sanguínea , Interleucina-1/sangue , Pré-Eclâmpsia/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/sangue , Inflamação/sangue , Pré-Eclâmpsia/sangue , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Adulto Jovem
6.
Trials ; 21(1): 468, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493441

RESUMO

OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4th 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bélgica , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Interações Hospedeiro-Patógeno , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Interleucina-1/antagonistas & inibidores , Interleucina-1/sangue , Interleucina-1/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Interleucina-6/imunologia , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/sangue , Receptores de Interleucina-6/imunologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
7.
Vascular ; 28(5): 629-642, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32366176

RESUMO

OBJECTIVES: Regulatory T cells (Tregs) mediate immunomodulation and protect against atherosclerosis. It is considered that reducing the amount of pro-inflammatory mediators could be achieved by enhancing the anti-inflammatory response, and this may be considered one of the main targets for therapy development. The inhibitory cytokines secreted by Tregs mainly include interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß). Based on its known immunosuppressive involvement with other inflammatory disorders, we hypothesized that the newly characterized cytokine interleukin-37 (IL-37) might be associated with the inhibitory functions of Treg in atherosclerosis. Immune regulatory functions of IL-37 have not been completely clarified. Accordingly, we speculated that IL-37 might play a regulatory role in the immunosuppression of Tregs in atherosclerotic disease. METHODS: Real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to test gene expression and protein levels of IL-37 in peripheral blood and localized freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease and 50 non-atherosclerotic subjects. Results were correlated to disease hallmarks. We also evaluated the ability of recombinant IL-37 to modulate Treg cytokine secretion and T cell inhibition in relation to atherosclerotic disorder in vitro.Results: Our results revealed that IL-37 was increased in patients with chronic lower limb atherosclerotic ischemia, compared to non-atherosclerotic controls. In addition, the expression levels of circulating IL-37 correlated with disease severity of chronic lower limb ischemia. Supplementation with rIL-37 augmented levels of released IL-10 and TGF-ß in supernatants of T cells co-cultured with Tregs in the enrolled patients.Conclusions: Results suggest a role for IL-37 in mediating anti-inflammatory functions in the atherosclerotic process, potentially involving enhancement of Treg inhibitory function and anti-inflammatory cytokine secretion with a particularly marked direct response in severe disease.


Assuntos
Interleucina-1/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Interleucina-1/genética , Interleucina-1/farmacologia , Interleucina-10/metabolismo , Isquemia/diagnóstico , Isquemia/imunologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/imunologia , Fenótipo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/metabolismo
8.
Surg Oncol ; 32: 99-107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31983439

RESUMO

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19+ B cells, while serum IL-37 seem to be associated with reduced percentage of CD3+CD8+ T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19+ B cells and CD3+ CD8+ T cells for OSCC progression.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/secundário , Interleucina-18/sangue , Interleucina-1/sangue , Leucócitos Mononucleares/patologia , Neoplasias Bucais/patologia , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Humanos , Interleucina-1/genética , Interleucina-18/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/cirurgia , Prognóstico , Taxa de Sobrevida
9.
Int J Med Sci ; 17(1): 71-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929740

RESUMO

It is known that high-intensity exercise can cause inflammation and damage in muscle tissue, and in recent years, physical therapists and fitness professionals have begun to use foam rolling as a recovery method to improve performance. Despite the lack of basic science studies to support or refute the efficacy of foam rolling, the technique is very widely used in the sports world. In this respect, we investigated whether foam rolling could attenuate muscle damage and inflammation. Female Wistar rats were assigned to control (C), foam rolling (FR), notexin without foam rolling (N) and notexin with foam rolling (NFR) groups. A 4.5 x 2 cm foam roller was used to massage their hind legs (two 60-second repetitions twice a day for 3 days). Motor function tests (Balance Beam Test and Grip strength) were used. We detected an increase in time and foot faults when crossing a beam in the N group compared to C and FR rats. In contrast, a significant decrease was detected in both tests in NFR compared to N rats. Muscle power was measured with a grip strength test and better performance was detected in NFR rats compared to N rats. Furthermore, an increase of pro-inflammatory proteins was noted in the N group, while there was a decrease in the NFR group. On the contrary, an increase in PPAR-γ (anti-inflammatory protein) in the NFR group compared to the N group demonstrates the anti-inflammatory properties of the foam rolling technique. In summary, applying foam rolling after damage has benefits such as an increase in anti-inflammatory proteins and a reduction of pro-inflammatory proteins, resulting in muscle recovery and better performance.


Assuntos
Inflamação/terapia , Força Muscular/fisiologia , Modalidades de Fisioterapia , Esportes/fisiologia , Animais , Modelos Animais de Doenças , Venenos Elapídicos/toxicidade , Humanos , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Interleucina-1/sangue , Massagem , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Condicionamento Físico Animal/fisiologia , Fisioterapeutas , Amplitude de Movimento Articular/fisiologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
10.
J Am Acad Dermatol ; 82(2): 430-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31859047

RESUMO

BACKGROUND: T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored. OBJECTIVE: To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and ß-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap. METHODS: A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor-associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed. RESULTS: IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17 cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated psoriasiform dermatitis biopsy samples. LIMITATIONS: This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited. CONCLUSIONS: In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions.


Assuntos
Erupção por Droga/sangue , Erupção por Droga/complicações , Eczema/sangue , Eczema/complicações , Interleucina-17/sangue , Interleucina-1/sangue , Psoríase/sangue , Psoríase/complicações , Células Th17 , Células Th2 , Fator de Necrose Tumoral alfa/antagonistas & inibidores , beta-Defensinas/sangue , Adolescente , Adulto , Idoso , Biópsia , Criança , Erupção por Droga/etiologia , Erupção por Droga/patologia , Eczema/imunologia , Eczema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/patologia , Estudos Retrospectivos , Adulto Jovem
11.
PLoS One ; 14(12): e0225556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31821340

RESUMO

BACKGROUND: Currently, there are serious limitations in the direct diagnosis of active tuberculosis (ATB). We evaluated the levels of the IL-18/IL-37/IP-10 signalling complex proteins in Mycobacterium tuberculosis (M.tb)-specific antigen-stimulated QuantiFERON® Gold In-Tube (QFT) cultures and in serum samples from ATB patients, healthy individuals with latent M.tb infection (LTBI) and healthy controls (HC) to examine whether combined analyses of these proteins were useful in the differentiation of M.tb states. METHODS: The concentrations of IL-18, IL-18BP, IFN-γ, IL-37 and IP-10 in the serum and QFT supernatants were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. Free IL-18 levels were calculated using the law of mass action. RESULTS: Increased concentrations of total and free IL-18, IL-18BP, IFN-γ and IP-10 in the sera of ATB patients were detected. These increases were not counterbalanced by the overproduction of IL-37. Complex co-expression of serum IL-18BP and IL-37, IP-10 and IFN-γ was identified as the highest discriminative biomarker set for the diagnosis of ATB. CONCLUSIONS: Our results suggest that the IL-18 signalling complex might be exploited by M. tuberculosis to expand the clinical manifestations of pulmonary TB. Therefore, direct analysis of the serum components of the IL-18/IL-37 signalling complex and IP-10 may be applicable in designing novel diagnostic tests for ATB.


Assuntos
Quimiocina CXCL10/sangue , Interleucina-18/sangue , Interleucina-1/sangue , Tuberculose Latente/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interferon gama/sangue , Interferon gama/imunologia , Tuberculose Latente/sangue , Tuberculose Latente/imunologia , Masculino , Pessoa de Meia-Idade , Polônia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/imunologia , Adulto Jovem
12.
Molecules ; 25(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861585

RESUMO

We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that "higher" levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Interleucina-1/sangue , Interleucina-1/genética , Esclerose Múltipla/tratamento farmacológico , Adulto , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Simulação por Computador , Progressão da Doença , Doenças em Gêmeos/tratamento farmacológico , Doenças em Gêmeos/genética , Doenças em Gêmeos/imunologia , Feminino , Cloridrato de Fingolimode/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Recidiva , Gêmeos Monozigóticos/genética , Regulação para Cima
13.
PLoS One ; 14(11): e0224615, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31675372

RESUMO

To investigate in datasets of immunologic parameters from early-onset and late-onset periodontitis patients (EOP and LOP), the existence of hidden random fluctuations (anomalies or noise), which may be the source for increased frequencies and longer periods of exacerbation, resulting in rapid progression in EOP. Principal component analysis (PCA) was applied on a dataset of 28 immunologic parameters and serum IgG titers against periodontal pathogens derived from 68 EOP and 43 LOP patients. After excluding the PCA parameters that explain the majority of variance in the datasets, i.e. the overall aberrant immune function, the remaining parameters of the residual subspace were analyzed by computing their sample entropy to detect possible anomalies. The performance of entropy anomaly detection was tested by using unsupervised clustering based on a log-likelihood distance yielding parameters with anomalies. An aggregate local outlier factor score (LOF) was used for a supervised classification of EOP and LOP. Entropy values on data for neutrophil chemotaxis, CD4, CD8, CD20 counts and serum IgG titer against Aggregatibacter actinomycetemcomitans indicated the existence of possible anomalies. Unsupervised clustering confirmed that the above parameters are possible sources of anomalies. LOF presented 94% sensitivity and 83% specificity in identifying EOP (87% sensitivity and 83% specificity in 10-fold cross-validation). Any generalization of the result should be performed with caution due to a relatively high false positive rate (17%). Random fluctuations in immunologic parameters from a sample of EOP and LOP patients were detected, suggesting that their existence may cause more frequently periods of disease activity, where the aberrant immune response in EOP patients result in the phenotype "rapid progression".


Assuntos
Periodontite Agressiva/imunologia , Adulto , Periodontite Agressiva/etiologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Estudos de Casos e Controles , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon gama/sangue , Interleucina-1/sangue , Interleucina-4/sangue , Pessoa de Meia-Idade , Análise de Componente Principal , Fatores de Risco , Adulto Jovem
14.
Clin Cardiol ; 42(10): 942-951, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415103

RESUMO

BACKGROUND: Interleukin-1 (IL-1) played a role in the occurrence and development of atherosclerosis and cardiovascular events. However, the association between IL-1 blockage treatment and reducing of cardiovascular risk remains poorly defined. HYPOTHESIS: IL-1 blockage treatment reduce the risk and incidence rate of overall major adverse cardiovascular events (MACE), all-cause death, acute myocardial infarction(MI), unstable angina and heart failure. METHODS: We performed a search of published reports by using MEDLINE database (January 1, 2005 to April 1, 2018). The randomized controlled trials (RCTs) that reported sample size and occurrence numbers in test group and placebo group for the associations of interest were included. RESULTS: Eight RCT studies involving 15 647 participants were identified. Compared with those who took no IL-1 blockage, patients taking IL-1 blockage experienced a decreased risk of overall MACE (RR 0.88, 95% CI 0.82-0.94), unstable angina (RR 0.80, 95% CI 0.66-0.98), and breakthrough or recurrence of heart failure (RR 0.44, 95% CI 0.22-0.87). No association was found between IL-1 blockage treatment and death from all cause (RR 0.91, 95% CI 0.83-1.00) as well as acute MI (RR 0.85, 95% CI 0.71-1.01). The RRs associated with overall MACE, death from all cause, acute MI, and unstable angina for anakinra were 1.05, 1.16, 2.97, and 0.56, respectively, and for canakinumab were 1.05, 0.91, 0.80, and 0.80, respectively. CONCLUSIONS: Administration of IL-1 blockage was associated with decrease risks of overall MACE, unstable angina, and breakthrough or recurrence of heart failure, but not with death from all cause as well as acute MI.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1/antagonistas & inibidores , Proteínas Recombinantes de Fusão/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Saúde Global , Humanos , Incidência , Interleucina-1/sangue , Fatores de Risco
15.
Stem Cell Res ; 39: 101525, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31430719

RESUMO

Keratoconjunctivitis sicca (KCS) is of predominantly immune-mediated origin. Dogs are an excellent model for understanding this disease, as the origin of KCS in dogs is like that in humans. The objective of this study was to localize and quantify immunological markers, such as CD4 lymphocytes, interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα), before and after topical treatment with mesenchymal stem cells (MSCs). Twenty-two dogs positive for KCS were topically treated with 50 µL (1 × 106 MSCs) in the conjunctival sac and were evaluated for 6 months. The levels of the markers CD4, IL-6, IL-1 and TNFα were analyzed in conjunctival biopsy and cytology of the third eyelid gland by immunohistochemistry and immunocytochemistry. The results showed that before treatment, there was marked expression of all the markers (CD4, IL-6, IL-1 and TNFα), and after 6 months, there were significant (p < .05) reductions in the expression levels of all the markers. These results demonstrated that topical MSC treatment promotes a significant decrease in the expression levels of these inflammatory markers and could be used as adjuvant therapy in the treatment of KCS in dogs and humans. In addition, these markers can be excellent tools for diagnosing and analyzing the progression of KCS.


Assuntos
Antígenos CD4/sangue , Interleucina-1/sangue , Interleucina-6/sangue , Ceratoconjuntivite Seca/sangue , Ceratoconjuntivite Seca/terapia , Células-Tronco Mesenquimais/fisiologia , Fator de Necrose Tumoral alfa/sangue , Administração Tópica , Animais , Cães , Síndromes do Olho Seco/sangue , Síndromes do Olho Seco/terapia , Feminino
16.
Vasc Health Risk Manag ; 15: 209-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371977

RESUMO

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.


Assuntos
Aterosclerose , Colesterol/sangue , Embolia de Colesterol , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cristalização , Embolia de Colesterol/sangue , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/epidemiologia , Embolia de Colesterol/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Síndrome
17.
BMC Neurol ; 19(1): 185, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382910

RESUMO

BACKGROUND: Interleukin 36 (IL-36) cytokines belong to the IL-1 family and play an important role in some autoimmune diseases. However, the relationship between IL-36 and neuromyelitis optica spectrum disorders (NMOSD) remains unclear. METHODS: We determined serum IL-36α, IL-36ß and IL-36γ levels and assessed correlations with clinical characteristics in 50 NMOSD patients and 30 healthy controls (HC). RESULTS: The concentrations of serum IL-36ß and IL-36γ were significantly higher in patients with NMOSD than in HCs and decreased during remission. Serum IL-36ß levels were positively correlated with the annual relapse rate (ARR), spinal cord lesion length and Expanded Disability Status Scale (EDSS) scores. CONCLUSIONS: Serum IL-36ß and IL-36γ levels were related to disease activity in NMOSD patients and may be important biomarkers of NMOSD.


Assuntos
Biomarcadores/sangue , Interleucina-1/sangue , Interleucina-1/imunologia , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Coll Physicians Surg Pak ; 29(7): 644-648, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31253216

RESUMO

OBJECTIVE: To compare effect of proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) internal fixation on serum inflammatory mediators (CRP, IL-1, IL-6 and TNF-α), myocardial injury markers (cTnT, CK-MB), and Myo-heart failure marker (BNP) in elderly patients with intertrochanteric fractures. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical University, China, from January 2016 to February 2018. METHODOLOGY: A total of 114 patients with intertrochanteric fractures were randomly divided into Group A and Group B, with 57 cases in each group. Group A was treated with PFNA and Group B with DHS internal fixation. Serum CRP, IL-1, IL-6, TNF-α, cTnT, CK-MB, Myo, BNP and surgical indication were compared. RESULTS: Operation time and weight-bearing time in Group A were shorter than Group B (both p<0.001). Intraoperative blood loss and postoperative drainage volume in Group A were lower than Group B (both p<0.001). On the 7ᵗʰ day after surgery, serum CRP, IL-1, IL-6, TNF-α, cTnT, CK-MB, Myo and BNP in Group A were lower than Group B (all p<0.001). CONCLUSION: Compared with DHS, PFNA effectively reduced serum inflammatory mediators with less damage to cardiac function and myocardium in elderly patients with intertrochanteric fractures.


Assuntos
Pinos Ortopédicos , Parafusos Ósseos , Fixação Interna de Fraturas/instrumentação , Fraturas do Quadril/sangue , Fraturas do Quadril/cirurgia , Fatores Etários , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Creatina Quinase Forma MB/sangue , Feminino , Humanos , Interleucina-1/sangue , Interleucina-6/sangue , Masculino , Peptídeo Natriurético Encefálico/sangue , Troponina T/sangue , Fator de Necrose Tumoral alfa/sangue
19.
PLoS One ; 14(5): e0217800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150497

RESUMO

OBJECTIVE: Studies have suggested that arginine vasopressin (AVP) and its surrogate marker copeptin increase during exercise, independently of serum sodium and/or osmolality. In extreme cases, this can lead to runners-induced hyponatremia. Interleukin-1 (IL-1) increases during exercise and induces AVP in animal models. We here therefore investigate whether copeptin (a surrogate marker for AVP) increases upon exercise in young and healthy males, and whether this increase is regulated by IL-1. DESIGN: In a randomized, placebo-controlled, double-blind, crossover trial in 17 healthy male volunteers, the effect of the IL-1 receptor antagonist anakinra on exercise-induced copeptin was compared with placebo. METHODS: Participants exercised for one hour at 75% of VO2max and were not allowed to drink/eat 6 hours before and during the study. Participants received either 100 mg of anakinra or placebo 1h before exercise. Blood was drawn at certain time intervals. RESULTS: In both groups, copeptin levels were induced by 2.5-fold upon exercise (p<0.001), from 4.5-10.6 pmol/l in the placebo, and 4.3-11.3 pmol/l in the anakinra group, (p = 0.38). One hour after exercise, copeptin levels dropped to 7.7 and 7.9 pmol/l in the placebo and anakinra group, respectively (p = 0.58). The increase of copeptin levels was not explained by sodium concentrations. CONCLUSIONS: Exercise induces a continuous rise of plasma copeptin levels in healthy male volunteers independently of sodium levels and fluid intake. This increase is not regulated by the IL-1 pathway.


Assuntos
Arginina Vasopressina/sangue , Exercício Físico/fisiologia , Glicopeptídeos/sangue , Interleucina-1/sangue , Adulto , Método Duplo-Cego , Humanos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Concentração Osmolar , Corrida/fisiologia , Sódio/sangue
20.
J Biol Regul Homeost Agents ; 33(3): 889-894, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184089

RESUMO

Wheezing is a common symptom of respiratory diseases. A survey found that about 1/3 of all children had at least one episode of wheezing before reaching the age of 3, and about 1/2 of them had at least one episode of wheezing by the age of 6.


Assuntos
Asma/patologia , Interleucina-12/sangue , Interleucina-1/sangue , Interleucina-4/sangue , Vitamina D/sangue , Asma/sangue , Criança , Humanos , Sons Respiratórios
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