Interleukin-17 stimulates intraperitoneal neutrophil infiltration through the release of the chemokine GROα from peritoneal mesothelial cells

Full text

Introduction

IL-17 is a newly discovered cytokine implicated in the regulation of hematopoiesis and inflammation. Since IL-17 production is restricted to activated T lymphocytes the effects exerted by IL-17 may help 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.

Methods

Leukocyte infiltration in vivo was assessed in BalB/ CJ mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC).

Results

Intraperitoneal administration of IL-17 resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human GROα). Pre-treatment with anti-KC antibody significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROα mRNA and protein. Combination of IL-17 together with TNFα resulted in an increased stability of GROα mRNA and synergistic release of GROα protein. Anti-IL-17 antibody blocked the effects of IL-17 in vitro and in vivo.

Conclusions

IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.