IntroductionInterleukin-17 (IL-17), originally identified by Rouvier et al 1 as cytolytic T-lymphocyte (CTL)-associated antigen 8, is a T-cellderived cytokine with homology to Herpesvirus saimiri. [1][2] It is expressed mainly by activated CD4 ϩ CD45RO ϩ memory T cells. [3][4] CD4 T cells can be classified into T-helper (Th) 1 cells, which secrete interferon (IFN) ␥, IL-2, and tumor necrosis factor (TNF) ␤; Th2 cells, which produce IL-4, IL-5, IL-6, IL-10, and IL-13; and Th0 cells, a common precursor with the ability to release both IFN␥ and IL-4. Thirty percent of Th0/Th1 clones have been shown to produce IL-17, whereas Th2 clones never express IL-17. 5 IL-2 and IL-15 were found to increase IL-17 production by human peripheral blood (PB) mononuclear cells. 6 IL-17 is considered to be a proinflammatory cytokine because it increases IL-6 and IL-8 production by macrophages, fibroblasts, keratinocytes, and synovial cells 2,3,[7][8][9] and nitric oxide production by human osteoarthritic cartilage. 10,11 IL-17 also induces secretion of IL-1␤ and TNF-␣ by human macrophages and endothelial cells. 7,12 IL-17 activates the nuclear factor B and activator protein 1 transcription factors, which may explain its proinflammatory properties. 10,13 In addition, IL-17 induces production of granulocyte colony-stimulating factor and CXC chemokines that stimulate granulopoiesis and recruitment of neutrophils into tissues. [14][15][16] The IL-17 receptor is a type I transmembrane protein that is expressed in virtually all cells and tissues, in contrast to the restricted expression of IL-17, which is confined to T cells. 2,17 This receptor has no sequence similarity with any other known cytokine receptor. It interacts with the adapter molecule TNF receptorassociated factor 6, which is required for IL-17 signaling. 18 The exact role of IL-17 in disease is unknown. IL-17 has been found to promote cartilage destruction in various forms of arthritis. 19,20 Overproduction of IL-17 has been observed in the synovium of patients with rheumatoid arthritis 21 and in PB lymphocytes from patients with systemic sclerosis. 22 In a previous study, we found that IL-17 promotes tumorigenicity of human cervical tumors in nude mice. 23 Because this paradoxical tumor-promoting activity of IL-17 in the absence of T cells was unexpected, we conducted the current study to analyze the effect of IL-17 on the growth of syngeneic tumors in immunocompetent mice. We found that IL-17 inhibits the growth of 2 hematopoietic tumors, mastocytoma P815 and plasmocytoma Materials and methods Mice and tumor cell linesFemale Balb/c, DBA/2, and athymic nude/nude mice 6 to 8 weeks of age (Iffa Credo L'Arbresle, France) were used in this study. The mouse plasmocytoma J558L and mastocytoma P815 cell lines were obtained from the American Type Culture Collection (Manassas, VA). The mouse squamous cell carcinoma KLN 205 was purchased from the European Collection of Cell Culture (Salisbury, Wiltshire, United Kingdom). The cell lines were cultured in RPMI supplemented with 10% fet...

Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4 ؉ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3 ؉ CD4 ؉ CD45RO ؉ , a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.