Anti-inflammatory properties of interleukin-10 administration in hapten-induced colitis.
Therapeutic efficacy of interleukin-10 administration in colonic inflammation was assessed in rats. Following intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS), subcutaneous administration of 1-1000 micrograms/kg per day interleukin-10, or a placebo (0.9% NaCl) was commenced and continued for 5 days. Interleukin-10 administered at 1, 10 and 100 micrograms/kg per day significantly reduced myeloperoxidase activity by 34, 57, and 28%, respectively, compared to the placebo-treated group, which was paralleled by an attenuation of colonic tumor necrosis factor alpha (TNF-alpha) content. In contrast, the severity of mucosal necrosis was not affected by interleukin-10 administration at the dose range used. In addition, the 10-fold elevation in nitric oxide release, 5-fold rise in colonic nitrite production and enhanced expression of inducible nitric oxide synthase, associated with TNBS colitis, was not suppressed by interleukin-10. Interleukin-10 gene expression was elevated during the first 14 days of TNBS colitis. We conclude that 5 days administration of interleukin-10 in TNBS colitis displays mild anti-inflammatory properties which were not mediated via a nitric oxide-dependent pathway, but may involve TNF-alpha.
Ribbons
K A
KA
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112, USA.
Thompson
J H
JH
Liu
X
X
Pennline
K
K
Clark
D A
DA
Miller
M J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase