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 cytokinesFamilial Mediterranean fever (FMF) is the prototype of a group of hereditary inflammatory disorders. Patients experience short, self resolving, attacks of fever and serosal inflammation (peritonitis, arthritis, pleuritis). 1 Although between attacks patients totally recover clinically, biological markers of inflammation (Serum Amyloid A protein, C Reactive Protein) sometimes remain elevated. 2,3 The gene for this recessive disorder (MEFV) was identified 4 years ago by a positional cloning strategy. 4,5 Screening for MEFV mutations has provided the first specific tool for diagnosing FMF, which can now be differentiated from the various other inflammatory conditions. However, it has been proposed that some MEFV variants may predispose to inflammation in general, [6][7][8] and indeed, preferential association with other inflammatory conditions has been reported. [9][10][11] The function of MEFV is still unknown. The disease phenotype and the almost exclusive expression of MEFV in leukocytes suggest that the corresponding protein plays an important role in the inflammatory cascade. [12][13][14] Some inflammatory mediators such as cytokines have been shown to be involved in the pathogenesis of FMF. [15][16][17][18] The cytokine network has been studied in many circumstances in clinically diagnosed patients, ie during and between attacks, both on and off colchicine treatment, and after ex vivo induction, as well as in controls. The secreted levels of pro-inflammatory cytokines are enhanced during attacks, whereas during attack-free periods they do not differ or are slightly higher than in healthy subjects.The present study is the first investigation of cytokines (i) at the transcriptional level, and (ii) in genetically ascertained patients. We have compared messenger RNA (mRNA) levels of four pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-␣), interleukin 1 beta (IL-1), interleukin 6 (IL-6) and interleukin 8 (IL-8) in FMF patients in clinical remission and in healthy controls. TNF-␣ plays a key role in the inflammatory process by stimulating production of IL-1, which has a pyretic action; IL-6, promotes the release of acute phase reactants, and IL-8, is a chemoattractant.The FMF group comprised 44 patients, whose composition is shown in Table 1. 19 They were all in attack-free intervals upon blood sampling, based on clinical criteria: (i) no fever, no pain, no sign of inflammation, (ii) the time of their last attack was systematically documented, and happened at least 3 weeks earlier. The control group comprised 31 mutation-free healthy volunteers, unrelated to the patient group. We set up a multiplex RT-PCR strategy to quantify the cytokine mRNA levels relative to ...