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Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes
Raffaele Badolato,
Alessandro Negro Ponzi,
Maura Millesimo,
Luigi D. Notarangelo, and
Tiziana Musso
From the Clinica Pediatrica, Universita' di Brescia, Brescia; Dipartimento di Patologia e Medicina Sperimentale e Clinica, Universita' di Udine, Udine; and from Dipartimento di Sanita' Pubblica e di Microbiologia, Universita' di Torino, Torino, Italy.
Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the  and  components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15-contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon- (IFN-) and IL-4. IFN- inhibited IL-15-induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.
Blood, Vol. 90 No. 7 (October 1), 1997:
pp. 2804-2809
© 1997 by The American Society of Hematology.
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