Document 0398
 DOCN  M9550398
 TI    Differential modulation of T helper type 1 (Th1) and T helper type 2
       (Th2) cytokine secretion by prostaglandin E2 critically depends on
       interleukin-2.
 DT    9505
 AU    Hilkens CM; Vermeulen H; van Neerven RJ; Snijdewint FG; Wierenga EA;
       Kapsenberg ML; Department of Cell Biology and Histology, University of;
       Amsterdam, The Netherlands.
 SO    Eur J Immunol. 1995 Jan;25(1):59-63. Unique Identifier : AIDSLINE
       MED/95145553
 AB    Prostaglandin E2 (PGE2) favors T helper type 2 (Th2)-like cytokine
       secretion profiles in murine and human CD4+ T cells by inhibiting the
       production of the Th1-associated cytokines interleukin-2 (IL-2) and
       interferon-gamma (IFN-gamma) and up-regulating the production of the
       Th2-associated cytokines IL-4 and IL-5 in a dose-dependent way. However,
       the potent inhibition of IL-2 production by PGE2 seems to be in contrast
       with the simultaneous up-regulation of IL-4 and IL-5 production, because
       the induction of these cytokines requires IL-2. We, therefore,
       investigated to which extent the net modulatory effect of PGE2 is
       determined by the availability of IL-2. To this aim, we examined the
       effects of PGE2 on the cytokine secretion profiles of a panel of human
       Th0 clones upon stimulation via different activation pathways, resulting
       either in high or low IL-2 production. The differential modulation of
       Th1 and Th2 cytokines by PGE2 was observed only upon modes of
       stimulation resulting in high IL-2 production. When IL-2 production was
       low, PGE2 inhibited the secretion of all four cytokines. These different
       modulation patterns were directly related to the IL-2 availability,
       because (i) neutralizing antibody to IL-2 abrogated the up-regulatory
       effect of PGE2 on IL-4 and IL-5 secretion in experiments with high
       endogenous IL-2 levels, (ii) lack of differential cytokine modulation by
       PGE2 in conditions with low levels of endogenous IL-2 could be restored
       with exogenous IL-2, and (iii) cell viability was comparable in all
       conditions. These results demonstrate that the net modulatory effect of
       PGE2 on the cytokine secretion profile of T cells critically depends on
       the availability of IL-2. Since this parameter varies with the
       experimental conditions and the T cell population studied, this finding
       may explain why certain immune responses may be either up- or
       down-regulated by PGE2 under different conditions.
 DE    Animal  Clone Cells  Cytokines/*BIOSYNTHESIS  Dinoprostone/*PHYSIOLOGY
       Human  Interferon Type II/BIOSYNTHESIS
       Interleukin-2/BIOSYNTHESIS/PHYSIOLOGY  Interleukin-4/BIOSYNTHESIS
       Interleukin-5/BIOSYNTHESIS  Lymphocyte Transformation/IMMUNOLOGY  Mice
       Support, Non-U.S. Gov't  Th1 Cells/*IMMUNOLOGY  Th2 Cells/*IMMUNOLOGY
       JOURNAL ARTICLE

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