Pam. Vanleeuwen et al., PRETREATMENT WITH ENTERAL CHOLESTYRAMINE PREVENTS SUPPRESSION OF THE CELLULAR IMMUNE-SYSTEM AFTER PARTIAL-HEPATECTOMY, Annals of surgery, 221(3), 1995, pp. 282-290
Objective The authors tested the hypothesis that the beneficial effect
s of the endotoxin-binding agent cholestyramine on the postoperative c
ourse in rats that had undergone a partial hepatectomy was the result
of improvement of cellular immune functions. Summary Background Data M
ajor liver resection is associated with severe postoperative complicat
ions and a high incidence oi systemic infections. Gut-derived endotoxi
ns previously were shown to be involved in the pathogenic processes af
ter partial hepatectomy in rats. In addition, enteral cholestyramine i
mproved postoperative survival, but how its beneficial effects are med
iated is not clear. Methods Rats that were force-fed for 7 days with e
ither cholestyramine (150 mg/day) or 0.9% saline (equal volume) were r
andomized to undergo a partial hepatectomy or a sham operation. After
24 hours, the rats were killed and splenic mononuclear cells were test
ed in vitro for mitogenic responses and cytokine production.Results Pr
oliferative responses of splenic B and T lymphocytes and lipopolysacch
aride-stimulated production of tumor necrosis factor and interleukin-1
by splenocytes were lower in rats after partial hepatectomy than in s
ham-operated animals. An increased concanavalin A-stimulated productio
n of interleukin-2 also was found after partial hepatectomy compared w
ith sham levels. Pretreatment with enteral cholestyramine preserved ce
llular proliferative responsiveness of both B and T cells, and restore
d cytokine production by splenocytes to sham levels. Conclusion Prophy
lactic 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 auth
ors' results are consistent with the hypothesis that endotoxemia is in
volved in the pathogenesis of the cellular immune derangements after p
artial hepatectomy.