OKT3-Induced Cytokine Release Attenuation by Interleukin-10

ABSTRACT

Purpose: OKT3 is a very powerful immunosuppressive drug in acute allograft rejection treatment but its side-effects such as fever, nausea, vomiting, and pulmonary edema are strongly linked with its inducing cytokines such as tumor necrosis factor alphaTNF-alpha, interleukin-6(IL-6), and interferon-gammaIFN-gamma. Interleukin-10(IL-10) inhibits proinflammatory cytokines which are produced by activated monocyte/ macrophages and prevents production of cytokines in acute inflammatory states. The purpose of this study is to determine the effect of exogenous administration of the anti- inflammatory cytokine, IL-10 on TNF-alpha IL-6, and IFN-gammaproduction and pulmonary injury after OKT3 injection. METHODS: For experiment, Sprague-Dawley rat weighed 300~400 gm was injected either OKT3(0.6mg/kg i.v.) only or recombinant IL-10(0.5microgram/rat i.p. one hour before the injection of OKT3(IL-10/OKT3). The rats were divided into three groups; control group(n=5); normal saline injected group(1.0ml/rat i.v.), OKT3 group(n=5); OKT3 only injected group, and IL-10/OKT3 group; IL-10 plus OKT3 injected group. After two hours of injection, all animals were sacrificed and submitted for a study of serologic and histologic changes. Student t-test was used for statistical analysis. To evaluate the cytokine production the serum levels of TNF-alpha, IL-6, and IFN-gamma level were measured. The serum levels of TNF-alpha, IL-6, and IFN-gamma were also significantly decreased in IL-10/ OKT3 group(109.6+/-38.0, 65.2+/-14.1, 96.2+/-17.3pg/ml) compared with OKT3 group(399.8+/-71.4, 155.4+/-45.1, 297+/-87.0pg/ml)(p<0.05). To determine the pulmonary injury, wet/dry ratio and microscopic findings for the lung tissue were analyzed. RESULTS: The wet/dry ratio of the lung tissue was significantly decreased in IL-10 /OKT3 group (3.52+/-0.31) compared with OKT3 group(4.16+/-0.48)(p<0.05). Microscopic findings of lung tissue revealed severe neutrophilic infiltration and microvascular congestion in the OKT3 group, but in IL-10/ OKT3 group, neutrophilic infiltration and microvascular congestion were decreased. CONCLUSION: In this study the inhibitory effect of IL-10 on the production of proinflammatory cytokines by OKT3 treatment was significant. This results suggest that the exogenous IL-10 injection may decrease the complications associated with OKT3 treatment of allograft rejection in organ transplantation.