Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures

Familial Mediterranean fever (FMF) is an inherited disease whose manifestat ions are acute but reversible attacks of sterile inflammation affecting syn ovial and serosal spaces. The FMF gene (MEFV) was recently cloned, and it c odes for a protein (pyrin/marenostrin) homologous to known nuclear factors. We previously reported the deficient activity of a C5a/Interleukin (IL)-8 inhibitor, a physiologic regulator of inflammatory processes, In FMF serosa l and synovial fluids. We now describe the concomitant expression of MEFV a nd C5a/IL-8-inhibitor activity in primary cultures of human fibroblasts, Fi broblasts grown from synovial end peritoneal tissues displayed C5a/IL-8-inh ibitor activity that could be further induced with phorbol myristate acetat e (PMA) and IL-IP, Very low levels of chemotactic: inhibitor were evident i n skin fibroblast cultures or in peritoneal and skin fibroblasts obtained f rom FMF patients. MEFV was expressed in peritoneal and skin fibroblasts at a lower level than in neutrophils and could be further induced by PMA and I L-lp, In the FMF cultures, the MEFV transcript carried the M694V mutation, consistent with the genetic defect found in patients with this disease. MEN was also expressed in other cell lines that do not produce C5a/lL-8 inhibi tor. These findings suggest that human primary fibroblast cultures express MEFV and produce C5a/IL-8-inhibitor activity. The interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor requires further inves tigation.