Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways

IL-17 is a recently discovered cytokine that can be released from activated human CD4(+) T lymphocytes, This study assessed the proinflammatory effect s of human (h) IL-17 in the airways. In vitro, hIL-17 increased the release of IL-8 in human bronchial epithelial and venous endothelial cells, in a t ime and concentration-dependent fashion. This effect of hIL-17 was inhibite d by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha, In addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epi thelial-cells. Conditioned medium from hIL-17-treated bronchial epithelial cells increased human neutrophil migration in vitro. This effect was blocke d by an anti-hIL-8 Ab, In vivo, intratracheal instillation of hIL-17 select ively recruited neutrophils into rat airways. This recruitment of neutrophi ls into the airways was inhibited by an anti-hIL-17 Ab and accompanied by i ncreased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronch oalveolar lavage (BAL) fluid. The BAL neutrophilia was also blocked by an a nti-rMIP-2 Ab. The effect of hIL-17 on the release of hIL-8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively. Thes e data demonstrate that hIL-17 can specifically and selectively recruit neu trophils into the airways via the release of C-X-C chemokines from bronchia l epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways.