Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by fever and serosal inflammation accompanied with an outburst of acute phase inflammatory products and cytokines. We studied the role of T helper (Th) 1 and 2 cells in FMF to elucidate the character of the inflammation. The cytokine products of Th1 and Th2, interferon-g (IFN-g) and interleukin 4 (IL-4), respectively, were analyzed by intracellular cytokine staining and FACS analysis.
Methods: We studied 34 Turkish patients with FMF (18 asymptomatic, 8 during an attack, and 8 with amyloidosis) and 14 age matched controls, as well as 11 parents of the patients who were accepted as heterozygotes for MEFV (Familial Mediterranean gene) mutations. Peripheral blood mononuclear cells were isolated and stained with monoclonal antibodies for IFN-g and IL-4. The percentage of IL-4 positive T cells was not significantly different between the groups. However, the percentage of IFN-g positive T cells in FMF patients experiencing an attack (median 25.8%, range 8.9-50.5%) was significantly higher than asymptomatic FMF patients (median 12%, range 0.1-70.7) (p = 0.04) and age matched controls (n = 7, median 0.4%, range 0-3.9%) (p = 0.0001). The percentage of IFN-g positive T cells in asymptomatic FMF patients was also significantly higher than age matched controls (p = 0.008). Heterozygotes for FMF had significantly higher IFN-g production (median 2.6%, range 0-42.4%) compared to age matched controls (n = 7, median 0.2%, range 0-1.4) (p = 0.001). IFN-g production in FMF patients with secondary amyloidosis was also markedly increased but had a large range of variation.
Conclusion: Inflammation in FMF shows a Th1 polarization. We suggest that in patients with FMF the IFN-g concentrations may remain higher because the defective pyrin is not able to inhibit this Th1 mediated inflammation.