Interleukin-10 inhibits inducible nitric oxide synthase in an animal model of necrotizing enterocolitis.
BACKGROUND
Nitric oxide (NO) and its role in surgical inflammation are well documented; demonstrating the role of NO in necrotizing enterocolitis (NEC) and ways in which it may be suppressed may provide avenues for immune modulation in the treatment of NEC.


OBJECTIVE
We sought to demonstrate an increase in inducible nitric oxide synthase (iNOS) mRNA and nitric oxide in an experimental model of necrotizing enterocolitis. In addition, we hypothesized that interleukin-10 (IL-10) would attenuate this response.


METHODS
Newborn rats were treated with 25 microliters intraperitoneal IL-10 or vehicle prior to laparotomy, 1 h superior mesenteric artery (SMA) occlusion, 50 micrograms/kg intraluminal platelet activating factor administration, and SMA reperfusion. iNOS mRNA and nitric oxide levels were measured in the liver, small bowel, and serum and compared using Student's t-test.


RESULTS
Small bowel iNOS mRNA increased after NEC induction from 0.058 +/- 0.02 to 0.144 +/- 0.05 relative intensity units (RIU) at 2 h (p < 0.01) and from 0 to 0.09 +/- 0.02 RIU at 6 h (p < 0.03). Liver mRNA increased from 0.026 +/- 0.002 to 0.485 +/- 0.09 RIU (p < 0.002) and from 0 to 0.069 +/- 0.02 RIU (p < 0.0001) at 2 and 6 h, respectively. Serum nitric oxide increased in NEC induced animals at 2 h from 28.04 +/- 10.5 to 45.18 +/- 6.8 microM (p < 0.001). IL-10 suppressed iNOS mRNA and nitric oxide expression at 2 h in small bowel, liver, and serum by 60%, 89%, and 11%, respectively.


CONCLUSIONS
IL-10 decreases iNOS mRNA response in experimental NEC. This down-regulation may be an avenue for anti-inflammatory intervention in NEC.
Kling
K M
KM
UCLA, Sepulveda VA Department of Surgery, Los Angeles, CA 90095, USA.
Kirby
L
L
Kwan
K Y
KY
Kim
F
F
McFadden
D W
DW
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000503:physiopathology*; D016753:Interleukin-10 / Q000494:pharmacology*; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats
D016753:Interleukin-10; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat