Inactivation of interleukin-8 by the C5a-inactivating protease from serosal fluid

The complement fragment C5a and the cytokine interleukin-8 (IL-8) are proinflammatory peptides with potent chemotactic activity toward neutrophils. We have previously shown that C5a can be inactivated by a protease that is found in normal synovial and peritoneal fluids but is absent from serosal fluids obtained from patients with familial Mediterranean fever (FMF). We report here that serosal fluids can also eliminate the chemotactic activity of IL-8. The agent responsible for IL-8 elimination appears to be the C5a-inactivating protease, because the pure protease can inactivate IL-8, inactivation of IL-8 by normal peritoneal fluid is partly prevented by an antibody raised against the purified C5a-inactivating protease, and IL-8 is not inactivated by peritoneal fluids from patients with FMF. The ability of this protease to inactivate both, early (C5a) and late (IL-8) inflammatory mediators identifies it as a potentially significant regulator of inflammation.