Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.
Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2:IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS-induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. An imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.
Kandil
H M
HM
Center for Gastrointestinal Biology and Disease, Department of Medicine, The University of North Carolina at Chapel Hill, USA.
Argenzio
R A
RA
Sartor
R B
RB
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004760:Enterocolitis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D016595:Misoprostol / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012008:Recurrence; D012709:Serum Albumin / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D012709:Serum Albumin; D016595:Misoprostol; D009195:Peroxidase; D015232:Dinoprostone; D007213:Indomethacin