Augmented enhancement of in vitro production of inflammatory cytokines in peripheral blood mononuclear cells in patients undergoing simultaneous resection of the liver and gastrointestinal tract

Objective: To determine changes in the production of inflammatory cytokines and acute-phase proteins, and in the priming of peripheral blood mononucle ar cells (PBMC), as mechanisms for the high incidence of postoperative comp lications in patients who have undergone hepatectomy simultaneously with re section of the gastrointestinal tract. Design: Prospective, clinical study for 3 wks after operation. Setting: A surgical department in a university hospital. Patients: Twenty-one consecutive adult patients with synchronous and metach ronous hepatic metastases from gastrointestinal malignancies, curatively re sected by simultaneous resection (group A, n = 9) or by hepatectomy alone ( group B, n = 12), and 15 patients with gastrointestinal malignancies underg oing curative resection (group C). Intervention: Peripheral Venous blood samples collected be fore operation a nd on days 1, 3, 5, 7, 10, 14, and 21 after operation. Measurements and Main Results: The serum and plasma levels of acute phase p roteins, interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and endotoxin were measured. The in vitro production of IL-1 beta and TNF-a lpha by PBMC was also determined by the stimulation of lipopolysaccharide. The incidence of postoperative complications was significantly higher in gr oup A than in groups B and C. The serum levels of IL-6 increased significan tly, with a peak at postoperative day 1 in all groups, and the peak levels of IL-6 in groups A and B were significantly higher than that in group C. T he serum levels of all acute-phase proteins measured in this study (alpha(1 )-antitrypsin, haptoglobin, and C reactive protein) increased markedly afte r operation in group C (p < .05). In group A, only C reactive protein incre ased after operation, but its peak level was lower than in groups B and C ( p < .05). Although IL-1 beta and TNF-alpha in the serum were not detectable in any of the groups during the entire study period, the lipopolysaccharid e-induced in vitro production of IL-1 beta and TNF-alpha by PBMC in all gro ups was significantly elevated after operation, with a peak at days 1 and 3 after operation, respectively. In addition, the elevation of the in vitro production of IL-1 beta and TNF-alpha in group A was significantly greater than that in group C, lasting until postoperative day 5 (IL-1 beta) and pos toperative day 10 (TNF-alpha). The levels of plasma endotoxin increased sig nificantly in all groups, with a peak at day 1 after operation, and the pea k levels were significantly higher in group A than in groups B and C. There was a significant correlation between the peak levels of in vitro TNF-alph a production and the peak levels of plasma endotoxin (r(2) = .331, p < .01) , Conclusions: The augmented enhancement of the priming of PBMC as a result o f surgery in patients undergoing simultaneous resection of the liver and ga strointestinal tract, together with the reduced synthesis of the acute-phas e reactants and impaired host defense mechanisms, might be responsible for the high incidence of postoperative complications, possibly because subsequ ent exposure of primed macrophages/monocytes to triggering substances such as endotoxin and bacterial components after operation results in inappropri ate production of inflammatory cytokines.