OBJECTIVE: The authors tested the hypothesis that the beneficial effects of the endotoxin-binding agent cholestyramine on the postoperative course in rats that had undergone a partial hepatectomy was the result of improvement of cellular immune functions. SUMMARY BACKGROUND DATA: Major liver resection is associated with severe postoperative complications and a high incidence of systemic infections. Gut-derived endotoxins previously were shown to be involved in the pathogenic processes after partial hepatectomy in rats. In addition, enteral cholestyramine improved postoperative survival, but how its beneficial effects are mediated is not clear. METHODS: Rats that were force-fed for 7 days with either cholestyramine (150 mg/day) or 0.9% saline (equal volume) were randomized to undergo a partial hepatectomy or a sham operation. After 24 hours, the rats were killed and splenic mononuclear cells were tested in vitro for mitogenic responses and cytokine production. RESULTS: Proliferative responses of splenic B and T lymphocytes and lipopolysaccharide-stimulated production of tumor necrosis factor and interleukin-1 by splenocytes were lower in rats after partial hepatectomy than in sham-operated animals. An increased concanavalin A-stimulated production of interleukin-2 also was found after partial hepatectomy compared with sham levels. Pretreatment with enteral cholestyramine preserved cellular proliferative responsiveness of both B and T cells, and restored cytokine production by splenocytes to sham levels. CONCLUSION: Prophylactic treatment with enteral cholestyramine preserved cellular immune functions after partial hepatectomy in the rat, which may explain its beneficial effects on the postoperative course. Furthermore, the authors' results are consistent with the hypothesis that endotoxemia is involved in the pathogenesis of the cellular immune derangements after partial hepatectomy.
OBJECTIVE: The authors tested the hypothesis that the beneficial effects of the endotoxin-binding agent cholestyramine on the postoperative course in rats that had undergone a partial hepatectomy was the result of improvement of cellular immune functions. SUMMARY BACKGROUND DATA: Major liver resection is associated with severe postoperative complications and a high incidence of systemic infections. Gut-derived endotoxins previously were shown to be involved in the pathogenic processes after partial hepatectomy in rats. In addition, enteral cholestyramine improved postoperative survival, but how its beneficial effects are mediated is not clear. METHODS:Rats that were force-fed for 7 days with either cholestyramine (150 mg/day) or 0.9% saline (equal volume) were randomized to undergo a partial hepatectomy or a sham operation. After 24 hours, the rats were killed and splenic mononuclear cells were tested in vitro for mitogenic responses and cytokine production. RESULTS: Proliferative responses of splenic B and T lymphocytes and lipopolysaccharide-stimulated production of tumor necrosis factor and interleukin-1 by splenocytes were lower in rats after partial hepatectomy than in sham-operated animals. An increased concanavalin A-stimulated production of interleukin-2 also was found after partial hepatectomy compared with sham levels. Pretreatment with enteral cholestyramine preserved cellular proliferative responsiveness of both B and T cells, and restored cytokine production by splenocytes to sham levels. CONCLUSION: Prophylactic treatment with enteral cholestyramine preserved cellular immune functions after partial hepatectomy in the rat, which may explain its beneficial effects on the postoperative course. Furthermore, the authors' results are consistent with the hypothesis that endotoxemia is involved in the pathogenesis of the cellular immune derangements after partial hepatectomy.