Interleukin-4 enhances interferon-gamma synthesis but inhibits development of interferon-gamma-producing cells.
Interleukin-4 (IL-4) is antagonistic for many of the activities of interferon-gamma (IFN-gamma) and, as well as suppressing the development of T-helper type-1 (Th1) cells, has been reported to block directly the synthesis of IFN-gamma in human lymphocytes. However, IL-4 transgenic mice produce increased amounts of IFN-gamma as well as IL-4. We have compared the ability of rat IL-4 to regulate IFN-gamma secretion in short-term cultures of spleen cells with its effect on the differentiation of T lymphocytes into IFN-gamma-producing, or Th1-type, cells. Normal rat spleen cells were stimulated using a variety of mitogens and ovalbumin antigen, with or without IL-4, for 12-24 hr and the levels of IFN-gamma in the supernatants measured by enzyme-linked immunosorbent assay (ELISA). The results show that when normal rat splenocytes were stimulated with phytohaemagglutinin (PHA) or concavalin A (Con A), IL-4 enhanced secretion of IFN-gamma after 12-24 hr. This enhancement was also apparent when splenocytes from animals immunized 10 days previously with alum-precipitated ovalbumin were stimulated with ovalbumin in vitro, and appeared to be mediated primarily via CD+ T cells. In contrast, when spleen cells were maximally stimulated with phorbol myristate acetate (PMA) and ionomycin, addition of IL-4 had no effect on the amount of IFN-gamma secreted. When splenocytes were stimulated with Con A for 4 days in the presence of IL-4, and restimulated with PMA and ionomycin, IFN-gamma secretion was greatly suppressed. Our results indicate that IL-4 exerts differential effects on IFN-gamma secretion and on the development of IFN-gamma-producing lymphocytes.
Noble
A
A
Department of Allergy and Respiratory Medicine, United Medical School, Guy's Hospital, London.
Kemeny
D M
DM
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000939:Epitopes; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma