Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin-2

Eur J Immunol. 1995 Jan;25(1):59-63. doi: 10.1002/eji.1830250112.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clone Cells
  • Cytokines / biosynthesis*
  • Dinoprostone / physiology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / physiology
  • Interleukin-4 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Lymphocyte Activation / immunology
  • Mice
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Cytokines
  • Interleukin-2
  • Interleukin-5
  • Interleukin-4
  • Interferon-gamma
  • Dinoprostone