IL-18 Is a Potent Coinducer of IL-13 in NK and T Cells: A New Potential Role for IL-18 in Modulating the Immune Response

• Published in: The Journal of immunology (1950) 1999-05, Vol.162 (9), p.5070-5077
• Main Authors: Hoshino, Tomoaki, Wiltrout, Robert H, Young, Howard A
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - physiology; Animals; Cells, Cultured; Dose-Response Relationship, Immunologic; Drug Combinations; Humans; Interleukin-10 - biosynthesis; Interleukin-12 - pharmacology; Interleukin-13 - biosynthesis; Interleukin-18 - pharmacology; Interleukin-18 - physiology; Interleukin-2 - pharmacology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Mice, Transgenic; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.9.5070

IL-13 and IL-4 have similar biological activities and are characteristic of cytokines expressed by Th2 cells. In contrast, IL-12 and IL-18 have been shown to be strong cofactors for Th1 cell development. In this study, we found strong induction of IL-13 mRNA and protein by IL-2 + IL-18 in NK and T cells. In contrast, IL-12 did not enhance the IL-13 production induced by IL-2 alone. Moreover, IL-13 mRNA and protein expression induced by IL-2 + IL-18 in purified NK and T cells obtained from IFN-gamma knockout (-/-) mice were greater than seen in purified cells from normal controls. In contrast, IL-10 production induced by IL-2 and/or IL-12 was not significantly different in IFN-gamma (-/-) mice and normal controls. These results suggest IL-13 expression induced by IL-2 + IL-18 may be regulated by IFN-gamma in vivo, while IL-10 expression may be IFN-gamma-independent. Thus, depending upon the cell type, IL-18 may act as a strong coinducer of Th1 or Th2 cytokines. Our findings suggest that IL-12 and IL-18 have different roles in the regulation of gene expression in NK and T cells.