Prostaglandin E1 inhibits effector T cell induction and tissue damage in experimental murine interstitial nephritis.
Immunosuppressive effects of E-series prostaglandins have been demonstrated in many in vitro assays of immune responsiveness as well as in autoimmune diseases. To explore the mechanisms underlying prostaglandin E1 (PGE1)-associated immunosuppression in autoimmunity, we treated SJL mice immunized to produce immune-mediated interstitial nephritis with PGE1, PGF2 alpha, or vehicle alone. Mice receiving PGE1 treatment do not develop interstitial nephritis, nor do they display delayed-type hypersensitivity (DTH) to the immunizing renal tubular antigen preparation. The observed immunosuppression is critically dependent on PGE1 administration during the period of effector T cell induction. We therefore investigated the effect of PGE1 on the in vitro induction of DTH effector T cells reactive to renal tubular antigens (SRTA). PGE1 inhibits effector T cell induction in a dose-dependent, reversible manner, but has no inhibitory effect on fully differentiated DTH effector cells or SRTA-reactive cell lines. The PGE1 effect is indirect and mediated via nonspecific suppressor lymphokines. This suppression can be overcome by recombinant interleukin 1 (IL-1), which suggests a mechanism related to either diminished IL-1 secretion or target cell sensitivity to IL-1.
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D015237:Dinoprost; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007375:Interleukin-1 / Q000502:physiology; D007684:Kidney Tubules / Q000276:immunology; D051379:Mice; D009395:Nephritis, Interstitial / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D011460:Prostaglandins F / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000941:Antigens; D007375:Interleukin-1; D011460:Prostaglandins F; D011994:Recombinant Proteins; D015237:Dinoprost; D000527:Alprostadil