       Document 0483
 DOCN  M9610483
 TI    Interleukin-4 enhances interferon-gamma synthesis but inhibits
       development of interferon-gamma-producing cells.
 DT    9601
 AU    Noble A; Kemeny DM; Department of Allergy and Respiratory Medicine,
       United Medical; School, Guy's Hospital, London.
 SO    Immunology. 1995 Jul;85(3):357-63. Unique Identifier : AIDSLINE
       MED/96005825
 AB    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.
 DE    Animal  Base Sequence  Cells, Cultured  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY
       Epitopes/IMMUNOLOGY  Female  Interferon Type II/*BIOSYNTHESIS
       Interleukin-4/GENETICS/*PHARMACOLOGY  Lymphocyte Culture Test, Mixed
       Molecular Sequence Data  Rats  Rats, Inbred Strains  Rats, Wistar  RNA,
       Messenger/GENETICS  Spleen/IMMUNOLOGY  Support, Non-U.S. Gov't  Th1
       Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

