Suppression of acute inflammation by 15 methyl prostaglandin E1.
Prostaglandins are important regulators of inflammatory responses. The rat subcutaneous air pouch, a model for synovial inflammation, was used to study the effect of systemic injections of prostaglandin E1 (PGE1) and its stable analog 15S,15 methyl prostaglandin E1 (15M PGE1) on nonimmunologically induced acute inflammation. The 15M PGE1 analog was a more effective longer-lasting antiinflammatory agent. Acute inflammatory responses were induced with three diverse stimuli including monosodium urate crystals, leukotriene B4 and formylmethionylleucyl-phenylalanine. Animals were treated with 15 M PGE1 for 2 days before induction of inflammation. Analysis of pouch fluid 6 hours after injection of the inflammatory stimulus indicates that 15M PGE1 treatment suppressed exudate volume and protein concentration, polymorphonuclear leucocyte accumulation and activity of the lysosomal enzyme beta-galactosidase. Treatment with 15M PGE1 was least effective in preventing the fluid phase of inflammation (exudate volume and protein concentration) when leukotriene B4 was used to induce inflammation. Direct observation (dissecting microscope) of pouch lining vessels indicated that 15M PGE1 reduced markedly the intense vascular reactivity (increased number of dilated vessels and filamentous, corkscrew-shaped vessels) usually seen in an acute inflammatory response. The antiinflammatory effect of 15M PGE1 was also documented by histopathology of pouch lining tissue. Treatment with 15M PGE1 reduced substantially the invasion of pouch tissue by polymorphonuclear leucocytes which was induced by all three stimuli of inflammation. Results of these experiments show that systemic administration of 15M PGE1 is capable of suppressing acute inflammation induced by monosodium urate crystals, by the potent soluble naturally occurring mediator of inflammation leukotriene B4, and by the synthetic chemotactic peptide, formylmethionylleucylphenylalanine.
Tate
G A
GA
Department of Medicine, University of Pennsylvania, Philadelphia.
Mandell
B F
BF
Schumacher
H R
HR
Zurier
R B
RB
D000208:Acute Disease; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D007249:Inflammation / Q000188:drug therapy*; D007975:Leukotriene B4; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine; D051381:Rats; D011919:Rats, Inbred Strains; D014527:Uric Acid
D007975:Leukotriene B4; D014527:Uric Acid; C025170:15(S)-15-methylprostaglandin E1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000527:Alprostadil