Effect of Interleukin-10 on Pulmonary Injury in the Murine Model of Acute Visceral Ischemia

Roh, Sung Kyun; Kim, Dong Hwan; Kwun, Woo Hyung; Huh, Young Soo; Suh, Bo Yang; Kwun, Koing Bo

Abstract

BACKGROUND: Visceral ischemia-reperfusion produces injury both to the visceral organs that are made ischemic and to distant organs, such as the lung, that are not made ischemic. The pulmonary injury after visceral ischemia-reperfusion is, in part, a result of the production and release of a variety of humoral factors, such as proinflammatory cytokines, activated complements and lipid mediators. Two proinflammatory cytokines, tumor necrosis factoralpha (TNFalpha) and interleukin (IL)-1, have been implicated as early initiators of this response to visceral ischemia-reperfusion injury. Recently, additional concepts have been developed to block the synthesis and release of proinflammatory cytokines by using anti-inflammatory cytokine. Interleukin (IL)-10 inhibits proinflammatory cytokine which is produced by activated monocyte/ macrophages and prevents production of TNFalpha in acute inflammatory states. The purpose of this study is to determine the effect of exogenous administration of the anti-inflammatory cytokine, recombinant human IL-10, on proinflammatory cytokine production and pulmonary injury after visceral ischemia-reperfusion.
METHODS
Two hours before 25 minutes of supraceliac aortic clamp, ICR mouse which weighed 30-40 g were injected with 0.2 microgram and 2.0 microgram of recombinant human IL-10 intraperitoneally and classified into A and B treatment groups, respectively. A control group underwent 25 minutes of supraceliac aortic clamp, and then reperfusion only. A sham group underwent laparatomy only. Two hours after reperfusion, all animals were sacrificed and submitted for a study of serology and histologic changes. To determine the pulmonary injury, wet/dry ratio, tissue myeloperoxidase (MPO) assay of the lung were measured and the microscopic findings for the lung tissue were analyzed. To evaluate the change in the cytokine during study, murine serum TNFalpha level was also measured.
RESULTS
The wet/dry ratios of the lung tissue were significantly decreased in both IL-10 treatmentgroups (A and B treatment group) compared to the control group (p<0.05, p<0.05). The tissue MPO assays of the lung were significantly decreased in the IL-10 2.0 microgram treatment group (B treatment group) compared to the control group (p<0.05). The level of serum TNFalpha was also decreased in B treatment group compared to the control group (p<0.05). Microscopic findings revealed severe neutrophilic infiltration and microvascular congestion in the control group, but in both IL-10 treatment groups, neutrophilic infiltration and microvascular congestion were mild or moderate.
CONCLUSIONS
The inhibitory effect of IL-10 on pulmonary neutrophil infiltration and on the level of TNFalpha during visceral ischemia-reperfusion injury was significant in the experiment. The use of exogenous IL-10 may offer a new therapeutic approach for decreasing the complications associated with visceral ischemia-reperfusion.