title: Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes.
abstract: Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the beta and gamma 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-gamma (IFN-gamma) and IL-4. IFN-gamma 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.
authors.affiliation: Clinica Pediatrica, Universita' di Brescia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: A N
authors.initials: AN
authors.lastname: Ponzi
authors.forename: M
authors.initials: M
authors.lastname: Millesimo
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: T
authors.initials: T
authors.lastname: Musso
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D019409:Interleukin-15; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma