Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.
BACKGROUND
Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R.


METHODS
Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored.


RESULTS
Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion.


CONCLUSIONS
IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.
Lane
J S
JS
Department of Surgery, UCLA Medical Center 90095, USA.
Todd
K E
KE
Lewis
M P
MP
Gloor
B
B
Ashley
S W
SW
Reber
H A
HA
McFadden
D W
DW
Chandler
C F
CF
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007583:Jejunum / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D017538:Mesenteric Artery, Superior / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*
D016207:Cytokines; D016753:Interleukin-10