Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats.

ABSTRACT

BACKGROUND: Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes. MATERIALS AND METHODS: Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT followed by 2 h of rewarming. HT (31 ± 1°C) was induced using a cooling blanket and monitored via a rectal temperature probe. RESULTS: Survival duration was 2.78 ± 1.0 h in NT rats and 8.33 ± 0.32 h in HT rats (n = 8/group, P < 0.0001). In separate groups, 3 h after CLI, the spleen weight was significantly smaller in NT rats (769 ± 100 mg) than in HT rats (947 ± 157 mg, P = 0.04). Fluorescent immunostaining of formyl peptide receptors on leukocytes in spleen tissue showed considerably higher formyl peptide receptor expression in HT rats than in NT rats. Significantly elevated proinflammatory cytokines and myeloperoxidase enzyme in plasma were found in NT rats compared with HT rats. Anti-inflammatory cytokine, interleukin-10, was significantly higher in HT rats. Both proinflammatory cytokines and plasma myeloperoxidase were significantly reduced in splenectomized NT rats. CONCLUSIONS: Moderate hypothermic therapy significantly prolongs the survival duration of rats with severe septic shock. HT dampens the inflammatory response during septic shock by modulating the spleen to an anti-inflammatory mode and preventing the spleen from releasing activated splenic leukocytes into the blood.