S-34 Department of Rheumatology 1 , Ege Uni- versity School of Medicine; and Depart- ments of Internal Medicine 2 and Biochem- istry 3 , Dokuz Eylül University School of Medicine, Izmir, Turkey. Please address correspondence to: Selda Öktem, MD, Ege University School of Medicine, Department of Rheumatology, Bornova 35100, Izmir, Turkey. E-mail: seldaoktem@yahoo.com Received on June 19, 2003; accepted in revised form on January 22, 2004. Clin Exp Rheumatol 2004; 22 (Suppl. 34): S34-S36. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2004. Key words: Familial Mediterranean fever (FMF), IL-6, sIL-6R, FMF carriers. ABSTRACT Objective. Familial Mediterranean Fever (FMF) is a hereditary disease characterized by recurrent inflammato - ry attacks. A subclinical inflammation may persist in periods between the at - tacks and heterozygotes may have higher than normal levels of acute phase proteins. We investigated the lev - els of interleukin-6 (IL-6) and its solu - ble receptor (sIL-6R) in FMF patients and their obligatory carrier relatives. Methods. Serum levels of IL-6 and sIL- 6R were measured during acute attacks (n =18) and in attack-free FMF pa - tients (n = 26), obligatory carriers of FMF (n = 17) and normal controls (n = 11). Results. The median levels of IL-6 were significantly higher (45.71 pg/ mL, p = 0.001) during acute attacks of FMF only, and were normal (0.01 pg/ mL) in the other groups studied. There was no statistically significant differ - ence in the median sIL-6R values be - tween any of the groups (p = 0.22). Conclusion. IL-6 was extremely eleva - ted during FMF attacks but could not detect hypothetical “subclinical” in - flammation during attack-free intervals or in the heterozygote relatives of pa - tients. Serum levels of sIL-6R were comparable in all four groups. Introduction Familial Mediterranean fever (FMF) is an autosomal recessive disease charac- terized by recurrent inflammatory at- tacks of the serosal membranes (1). The disease is caused by mutations in a gene named MEFV, which encodes a protein called pyrin or marenostrin (2, 3). This protein may play an important role in inflammatory pathways and in the regulation of apoptosis of neutro- phils (4). The acute attacks are often accompanied by increased plasma con- centrations of a group of acute phase proteins, including C-reactive protein (CRP), serum amyloid A (SAA) and fi- brinogen, and elevations of these pro- teins are supportive criteria for the dia- gnosis of FMF (5). The acute phase proteins may remain somewhat elevat- ed in certain patients during the attack- free intervals and they may also be above normal in heterozygous carriers of the disease (6-8). IL-6 is the chief stimulator of the production of most acute phase proteins and may play a major role in acute attacks of FMF (9- 11). The soluble receptor of IL-6 (sIL- 6R) is present in the circulation and in- flammatory body fluids; it may play an independent role while enhancing the activity of IL-6 (12-14). We measured the serum levels of IL-6 and its soluble receptor (sIL-6R) during acute attacks and attack-free periods in FMF patients and their obligatory carrier (heterozy- gote) relatives. Materials and methods All of the patients fulfilled the diagnos- tic criteria for FMF (5) and were on regular colchicine treatment. Informed consent approved by the ethical com- mittee of our institute was obtained from each patient. Serum levels of IL-6 and sIL-6R were studied in the venous blood samples ta- ken from 18 adult FMF patients during 27 individual acute attacks, and from 26 attack-free FMF patients, 17 obli- gatory heterozygote relatives (parents and siblings) and 11 healthy controls. Four patients were seen during more than one attack (5 separate attacks in 1 patient, 4 separate attacks in one pa- tient and 2 separate attacks in 2 pa- tients). Blood samples from FMF pa- tients suffering acute attack were taken during the first 4-6 hours of the attack period. All venous blood samples, which were obtained from the antecu- bital vein, were transported in an ice Levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in familial Mediterranean fever (FMF) patients and their first degree relatives S. Öktem 1 , T.U. Yavuzsen 2 , B. Sengül 2 , H. Akhunlar 3 , S. Akar 2 , M. Tunca 2