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.
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.
Hoshino
T
T
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick Cancer and Research Development Center, MD 21702, USA.
Wiltrout
R H
RH
Young
H A
HA
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D018793:Interleukin-13 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000494:pharmacology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D018793:Interleukin-13; D020382:Interleukin-18; D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12