Interferon-gamma improves muscle flap microcirculation in double-strand RNA-induced inflammation

Endothelial cell (EC) activation and subsequent expression of leukocyte adh esion molecules are initial events in multiple pathological processes. Vira l double-strand ribonucleic acid (dsRNA) induces EC adhesion protein expres sion and leukocyte adhesion in vitro. Interferon-gamma (IFN-gamma) has been demonstrated to modulate the expression of certain adhesion proteins. The purpose of this study was to measure the inflammatory response to a viral m imetic-a synthetic dsRNA, polyinosinic-polycytidylic acid (poly-I:C)-on the microcirculation of a muscle flap in a rat model and to determine whether IFN-gamma attenuated the response, Two-stage surgery to create a cremaster muscle end-organ tube flap was performed on 18 male Sprague-Dawley rats in three groups. After intra-arterial injection into the abdominal aorta, the reagents (phosphate-buffered saline-bovine serum albumin [PBS-BSA] in group s I and II, and IFN-gamma in group III) were kept for 1 hour in this end-or gan system. During the second stage at 16 hours, after injection into the p enile vein (PBS-BSA in group I, poly-I:C in groups II and III), the flap wa s prepared for intravital microscopic measurement. The following parameters were measured: red blood cell velocity; vessel diameter; number of functio nal capillaries; and number of rolling, sticking, and transmigrating neutro phils and lymphocytes. Wilcoxon's rank sum test was used for statistical co mparison. Poly-I:C caused a 70% increase in the main artery diameter and a 7% increase in velocity. But as a consequence of dynamic activation of leuk ocyte interaction, a 30% drop in functional capillary perfusion was observe d. Injury to the entire vascular endothelium was confirmed by a 160% increa se in transmigrating leukocytes. Treatment with IFN-gamma inhibited the pol y-I:C-induced inflammation, as shown by 88%, 63%, and 85% decreases in roll ing, sticking, and transmigrating leukocytes respectively, and by a 28% inc rease in capillary perfusion. Treating the system with IFN-gamma in advance , inhibited poly-I:C-induced inflammation, shown by marked decreases in rol ling, adhering, and transmigrating leukocytes, and a notable increase in pe rfused capillaries, These observations reflect an inhibitory effect of IFN- gamma on leukocyte adhesion molecule expression in vascular endothelium in response to dsRNA in a muscle flap at the microcirculatory level.