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Low Endogenous Prostaglandin E2 Predisposes to Relapsing Inflammation in Experimental Rat Enterocolitis

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Abstract

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-α (TNF-α) 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 μg/g) or human serum albumin intramurally. Tissue IL-1α and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1α ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1α concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1α and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1α (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. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

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Authors and Affiliations

  1. Center for Gastrointestinal Biology and Disease, Department of Medicine, Division of Digestive Diseases and Nutrition, The University of North Carolina, Chapel Hill

    Hossam M. Kandil, Robert A. Argenzio & R. Balfour Sartor

  2. North Carolina State University, Raleigh, North Carolina

    Hossam M. Kandil, Robert A. Argenzio & R. Balfour Sartor

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Kandil, H.M., Argenzio, R.A. & Sartor, R.B. Low Endogenous Prostaglandin E2 Predisposes to Relapsing Inflammation in Experimental Rat Enterocolitis. Dig Dis Sci 45, 2091–2099 (2000). https://doi.org/10.1023/A:1026675005554

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