Proposed mechanism of the inflammatory attacks in familial Mediterranean fever.

Peritoneal and synovial fluids of patients with familial Mediterranean fever lack a protein that inhibits neutrophil chemotaxis by antagonizing the complement-derived inflammatory mediator C5a. The C5a inhibitor activity was studied with the use of a C5a binding assay where peritoneal fluids were tested for their ability to inhibit recombinant C5a binding to dibutyryl cyclic adenosine monophosphate-induced U937 cells. In contrast to normal peritoneal fluids, those from patients with familial Mediterranean fever contained less than 1% C5a inhibitor activity. Gel filtration and ion exchange chromatography of peritoneal fluids from those patients did not yield any fraction that inhibited C5a binding. We suggest that the serosal tissue of patients with familial Mediterranean fever is devoid of C5a inhibitor activity and that this deficiency may explain in part the local inflammatory episodes characteristic of this disease.