Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activa ted human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Bec ause IL-6 and IL-8 have been implicated in the pathogenesis of cervical can cer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL -8 secretion by cervical carcinoma cell lines at both protein and mRNA leve ls. No direct effect of IL-17 on in vitro proliferation of cervical tumor c ell lines could be demonstrated. However, two cervical cell lines transfect ed with a cDNA encoding IL-17 exhibited a significant increase in tumor siz e as compared to the parent tumor when transplanted in nude mice This enhan ced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supporte d by its expression on the cervical tumor in patients with CD4 infiltration . IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports conce rning the deleterious effect of CD4 T cells in cancer.