Plasma interleukin-10 and interleukin-12 levels in patients with familial Mediterranean fever.
ABSTRACT Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, polyserositis and arthritis. A vast array of cytokines were analysed in these patients, however, little is known about the pro-inflammatory cytokine interleukin (IL)-12. Plasma IL-12 and IL-10 were measured in 24 patients with FMF (19 active, 5 inactive) and 18 healthy controls by ELISA. From 15 active patients blood was also drawn in attack-free period. Mean plasma IL-12 levels of the FMF patients (mean +/- SEM, 6.84+/-3.59 pg/ml) were higher than the controls (0.13+/-0.09 pg/ml, P < 0.001). Mean IL-12 levels of active (7.02+/-5.23 pg/ml) and inactive patients (6.89+/-5.61 pg/ml) were comparable, and they were higher compared to controls (P < or = 0.001). Mean plasma IL-10 levels of the total FMF patients (3.01+/-1.53 pg/ml) were also higher than the controls (P = 0.024). Patients had higher IL-10 levels in attacks (3.83+/-2.02 pg/ml) compared to levels when they were in remission (1.86+/-1.59 pg/ml, P = 0.046). Significantly elevated IL-12 levels in FMF patients regardless of activity may suggest the presence of a pro-inflammatory state also in the inactive period of FMF. Significant increase in IL-10 levels in FMF group may point to the compensatory suppression of inflammation in active periods of the disease.
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ABSTRACT: Introdução colchicina é a viga-mestra para o tratamento de FFM, que é uma doença autoinflamatória com polisserosite recidivante como principal manifestação. Apesar de doses diárias de 2 mg ou mais/dia, aproximadamente 5%-10% dos pacientes continuam a sofrer de seus ataques. Neste estudo, objetivamos investigar os aspectos da depressão e dos ataques em pacientes com FFM apresentando resistência à colchicina (RC). Pacientes e Métodos em pacientes com FFM, RC foi definida como dois ou mais ataques nos últimos seis meses, quando em medicação com colchicina 2 mg/dia. Dezoito pacientes (nove mulheres e nove homens) foram recrutados no grupo RC e 41 pacientes no grupo de controle (29 mulheres/12 homens). Foram avaliados os achados demográficos, clínicos e laboratoriais, a fidelidade ao tratamento e os escores do Beck Depression Inventory (BDI). Resultados a idade de surgimento da FFM foi significativamente menor no grupo RC (12,3 anos vs. 16,9 anos, P = 0,03). A duração da doença foi maior no grupo RC (p = 0,01). Dores abdominais e nas pernas em decorrência do exercício foram significativamente mais frequentes no grupo RC versus controles (83% vs. 51%; p = 0,02 e 88% vs. 60%; p = 0,04, respectivamente). Pacientes com escores BDI > 17 pontos foram mais frequentes no grupo RC versus controles (50% vs. 34,1%; p < 0,001). Discussão verificamos que: (1) a idade do surgimento da doença foi mais baixa e (2) a duração da doença foi maior no grupo RC. Ataques pleuríticos, hematúria e proteinúria foram mais frequentes em pacientes com RC. Propomos que a depressão é fator importante a ser levado em consideração na sensibilidade à RC.09/2014; 54(5). DOI:10.1016/j.rbre.2014.03.022
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ABSTRACT: Introduction Colchicine is the mainstay for the treatment of FMF, which is an auto‐inflammatory disease mainly with relapsing polyserositis. Despite daily doses of 2 mg or more each day, approximately 5% to 10% of the patients continue to suffer from its attacks. In this study, we aimed to investigate the depression and attack features in patients with FMF who have colchicine resistance (CR). Patients e Methods CR was defined for FMF patients with 2 or more attacks within the last 6 months period while using 2 mg/day colchicine. Eighteen patients (9 Female/9 Male) were enrolled into the CR group and 41 patients were enrolled into the control group (12 Male/29 Female). Demographic, clinical e laboratory findings, treatment adherence, and the Beck Depression Inventory (BDI) scores were evaluated. Results the age of onset of FMF was significantly lower in the CR group (12.3 yrs vs. 16.9 yrs, P = 0.03). Disease duration was longer in the CR group (P = 0.01). Abdominal and leg pain due to exercise were significantly more frequent in the CR group versus controls (83% vs. 51%; P = 0.02 e 88% vs. 60%; P = 0.04, respectively). Patients with BDI scores over 17 points were more frequent in the CR group compared to controls (50% vs. 34.1%; P < 0.001). Discussion: we found that: (1) the age of disease onset was lower and (2) the disease duration was longer in CR group. Pleuritic attacks, hematuria e proteinuria were more frequent in CR patients. We propose that depression is an important factor to consider in the susceptibility to CR.Revista Brasileira de Reumatologia 09/2014; DOI:10.1016/j.rbr.2014.03.022 · 0.86 Impact Factor
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ABSTRACT: In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24 h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines’ involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.Cytokine 10/2014; 69(2):248–254. DOI:10.1016/j.cyto.2014.06.012 · 2.87 Impact Factor