Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever.

Th1 type polarization has been implicated in the pathogenesis of familial Mediterranean fever (FMF). Interleukin-12 (IL-12) and IL-10 are proinflammatory cytokines, which play crucial role in Th1 and Th2 type immune response, respectively. IL-18 has a dual effect on T cell response: it was recognized as an IFN-gamma-inducing factor in T cells; acting in synergy with IL-12, leading to the development of Th1 type immune responses. But, in the absence of IL-12, IL-18 can promote the production of Th2 cytokines and take part in allergic inflammation. The aim of this study is to measure serum levels of IL-10, IL-12, and IL-18 in patients with FMF, and to investigate the relationship of their expressions with FMF attacks. Serum IL-10, IL-12, and IL-18 levels from patients with FMF were investigated. Thirty-one FMF patients with attack-free, 24 FMF patients with attack and 20 healthy controls were enrolled in the study. The levels of IL-10, IL-12p70 and IL-18 were measured by ELISA. Serum IL-10 levels were not different in FMF patients with attack and attack-free, and healthy controls. Serum IL-12 levels in FMF patients both with attack and attack-free were significantly higher than healthy controls (P = 0.002 and P = 0.047, respectively). There were no differences between FMF patients with attack and attack-free with regard to serum IL-12 levels. Serum IL-18 levels in FMF patients with attack and attack-free were significantly higher than healthy controls (P < 0.001 for both groups). With respect to serum IL-18 levels, no difference was found between FMF patients with attack and attack-free. Our results suggest that IL-12 and IL-18 contribute to the establishment of Th1 polarization seen in FMF and play a part in its pathogenesis. Detection of increased levels of IL-12 and IL-18 in patients with inactive disease implies that they seem to assist Th1 activation and subclinical inflammation persisting during the attack-free period of the disease.