Substance P levels in experimental ileitis in guinea pigs: effects of misoprostol.
Substance P, a neuropeptide mediator of inflammation, was quantified during the evolution of trinitrobenzene sulfonic acid (TNBS)-induced ileitis in guinea pigs. Ileitis was induced by a single intraluminal injection of TNBS (30 mg/kg in 50% ethanol). Misoprostol, a prostaglandin E1 analogue, was administered parenterally (30 mg/kg sc twice daily) in a group of TNBS-treated animals. Control guinea pigs received intraluminal saline (sham) or 50% ethanol (TNBS vehicle). Guinea pigs were evaluated at day 1, 3, 7, 14, or 30 after ileitis induction for substance P content (radioimmunoassay) and distribution (immunohistochemistry), morphology, myeloperoxidase (MPO) activity, and protein leak into the gut lumen. TNBS administration caused an increase in ileal MPO activity that peaked at day 7 and increased mucosal leak of protein. Misoprostol attenuated the granulocyte infiltration (MPO) response to TNBS but exacerbated the mucosal leak of protein. Substance P levels in whole ileal segments were unaltered from baseline on day 1 in all groups. On day 3 a marked decrease in ileal substance P content was evident in the TNBS and TNBS + misoprostol groups. As early as day 1, immunohistochemistry suggested that the decreased substance P content was confined to the mucosa and submucosa, because myenteric plexus staining was not reduced. Loss of staining in the perivascular nerves was particularly marked. Substance P content and distribution returned to baseline by day 30 post-TNBS, although MPO activity remained slightly elevated. We concluded that TNBS ileitis is associated with a marked reduction in mucosal and submucosal substance P content in parallel with the inflammatory response. Although misoprostol attenuated granulocyte infiltration in this model, it did not prevent the disturbances in enteric substance P or mucosal protein leak.
Miller
M J
MJ
Department of Pediatrics, School of Medicine, Louisiana State University, New Orleans 70112.
Sadowska-Krowicka
H
H
Jeng
A Y
AY
Chotinaruemol
S
S
Wong
M
M
Clark
D A
DA
Ho
W
W
Sharkey
K A
KA
D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D007079:Ileitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D016595:Misoprostol / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011863:Radioimmunoassay; D013373:Substance P / Q000378:metabolism*; D007507:Therapeutic Irrigation; D013997:Time Factors; D014018:Tissue Distribution; D014302:Trinitrobenzenesulfonic Acid
D011506:Proteins; D016595:Misoprostol; D013373:Substance P; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase