Interleukin-10 prevents loss of tone of rat skeletal muscle arterioles exposed to endotoxin

BACKGROUND: The anti-inflammatory cytokine interleukin-10 (IL-10) is known to inhibit the development of septic shock in animal models. This study was conducted to investigate the effect of IL-10 on the loss of vascular tone during exposure to endotoxin. Unlike numerous proinflammatory cytokines, the effects of IL-10 at the level of the microvasculature have not been previously studied. MATERIALS AND METHODS: First-order rat cremasteric arterioles (n = 27) were placed in an isolated vessel preparation and allowed to achieve spontaneous tone. An opened segment of thoracic aorta was then placed upstream from the arteriole in the superfusion line. The resistance arteriole of this in-series model, in contrast to the isolated arteriole alone, demonstrates a significant loss of tone when exposed to endotoxin. Following 1 h of equilibration in the presence or absence of IL-10 (20 ng/ml), the aorta and arteriole were then superfused with 2.5 microg/ml endotoxin or physiologic buffer for 60 min and serial arteriolar diameter measurements were recorded. Group 1 was exposed to endotoxin only, Group 2 was a time control, and Group 3 was pretreated with IL-10 prior to endotoxin exposure, while Group 4 was a control pretreated with IL-10 only. RESULTS: After the 60-min equilibration period there were no differences among the four groups in arteriolar tone. At t = 120 min, the percentage of tone in the control group was 43.6 +/- 3% (mean +/- SEM) and this was not changed by treatment with IL-10 (47.0 +/- 7% tone). Endotoxin alone caused arteriolar tone to fall to 31.4 +/- 3% (P < 0.05). However, endotoxin applied to arterioles pretreated with IL-10 was without effect (47.5 +/- 2%). CONCLUSIONS: Resistance arterioles pretreated with IL-10 maintain vascular tone during endotoxin exposure. We conclude that IL-10 pretreatment prevents loss of vascular tone of isolated arterioles exposed to endotoxin.