IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells

IL-17 is a newly discovered cytokine implicated in the regulation of hemopo iesis and inflammation, Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyt e infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on ch emokine generation in vitro were examined in human peritoneal mesothelial c ells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitme nt of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GRO alpha). Pretr eatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil a ccumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA, Exposu re of HPMC to IL-17 led to a dose- and time-dependent induction of GRO alph a mRNA and protein. Combination of IL-17 together with TNF-alpha resulted i n an increased stability of GROa mRNA and synergistic release of GRO alpha protein, Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo, I L-17 is capable of selectively recruiting neutrophils into the peritoneal c avity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.