15(s)-15-methylprostaglandin-e1 and Autoimmune-Diseases

Brown-Norway (BN) rats develop tubulointerstitial nephritis (TIN) after immunization with bovine tubular basement membrane (TBM) and adjuvants. Daily subcutaneous injections (either on Days 0-7 or Days 0-14) of (15S)-15-methyl prostaglandin E1 (M-PGE1) at a dose of 1 mg/kg/day markedly inhibited or completely abrogated the development of both the acute polymorphonuclear (Day 10) and the subsequent mononuclear (Day 14) inflammatory phases of BN rat TIN. Circulating anti-TBM antibody in Days 0-7 M-PGE1-treated rats was moderately diminished on Day 8 after immunization but not on Day 14. Circulating anti-TBM antibody in Days 0-14 M-PGE1-treated rats was only slightly diminished on Day 14. In experiments to test the effect of M-PGE1 on the elicitation phase of humorally mediated inflammation, M-PGE1 inhibited the acute inflammatory response observed 6 hours after intradermal injection of particulate TBM into TBM-sensitized BN rats. The inflammation in these skin tests was demonstrated by passive transfer experiments to be humorally mediated. The inhibition of acute humorally mediated intradermal inflammation was not attributable to neutropenia, because M-PGE1 caused a significant neutrophilia as demonstrated by peripheral blood smears. Although the inhibition of TIN in Days 0-14 M-PGE1-treated rats may have been due, in part, to dysfunction of the elicitation phase of humorally mediated inflammation, the inhibition of TIN in Days 0-7 M-PGE1-treated rats was more likely secondary to the diminished induction of either humoral or cellular immunity.

Topics: Alprostadil; Animals; Antibody Formation; Autoimmune Diseases; Basement Membrane; Cattle; Immunization; Inflammation; Kidney Tubules; Male; Nephritis, Interstitial; Rats; Rats, Inbred BN

MRL-lpr mice display immunoregulatory disturbances which are related to an early massive T-lymphocyte hyperplasia. Features of autoimmunity are rapidly progressive and these animals die from immune complex-mediated glomerulonephritis. Previous studies show that 15 methyl prostaglandin E1 (PGE) treatment in MRL-lpr mice prolongs survival by preventing lymphoproliferation and the subsequent renal disease. The present study indicates that a major activity of this therapy stabilizes several T-cell functions. Both the age-related loss of the autologous mixed-lymphocyte reaction (AMLR) (Ly1+ 2,3- dependent) and the concanavalin A-induced suppressor cell activity (Ly1- 2,3+ dependent) remain intact. It is suggested that PGE preserves these T-cell functions by maintaining a more normal balance of T-cell subsets.

Topics: Alprostadil; Animals; Antigen-Antibody Complex; Autoimmune Diseases; Cells, Cultured; Concanavalin A; Immunosuppression Therapy; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Prostaglandins E, Synthetic; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory