Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a recessively inherited inflammatory disorder, characterized by recurrent attacks of fever and serositis. Screening of mutations in the causing gene (MEFV) now allows accurate diagnosis of FMF among other inflammatory conditions. It is well documented that secreted levels of some pro-inflammatory cytokines are elevated in FMF. Here, we investigated cytokine expression at the transcriptional level, in patients that could be genetically ascertained. We have measured the transcript abundance of tumor necrosis factor alpha, interleukin-1beta, interleukin-6 and interleukin-8, in circulating leukocytes and shown that these were more elevated in attack-free FMF patients than in controls (P=0.01, P=0.008, P=0.02, P=0.001 respectively). There was no significant difference according to MEFV genotype or colchicine treatment. Our results suggest that cytokine transcriptional pathways are misregulated in attack-free FMF patients, and further supports the hypothesis that these patients have subclinical inflammation between attacks.