Modulation of helper T cell function by prostaglandins

Arthritis Rheum. 1994 Jun;37(6):925-33. doi: 10.1002/art.1780370623.

Abstract

Objective: To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transformating growth factor beta 1 by CD4+ T cells.

Methods: TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E1 (PGE1) analog misoprostol and PGE2. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays.

Results: PGE2 and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE2 are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, TH0-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells.

Conclusion: Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE2, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFN gamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Division / drug effects
  • Clone Cells / cytology
  • Clone Cells / drug effects
  • Clone Cells / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lymphokines / drug effects
  • Lymphokines / metabolism*
  • Misoprostol / pharmacology*
  • Molecular Sequence Data
  • Prostaglandins E / pharmacology*
  • RNA, Messenger / analysis
  • RNA, Messenger / drug effects
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • Interleukin-2
  • Interleukin-5
  • Lymphokines
  • Prostaglandins E
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Misoprostol
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor