The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenousbypass

Background. We have recently developed a simple method of hyperthermochemoh ypoxic isolated liver perfusion (HILP) as a regional therapy for unrecogniz ed liz,er micrometastases. However little is known about the influence of H ILP on cytokine production and liver function. We investigated the influenc e of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship, between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytok ines in the tumor response. Methods. Sixteen patients with metastatic liver tumors runs randomly assign ed to undergo hc;hepatectomy with HILP (group A, n = 9) or hepatectomy alon e (group, B, n = 7). The isolated liver was perfused for 30 minutes with Ri nger's lactate solution containing chemotherapeutic agents warmed to 42 deg rees C to 43 degrees C without oxygenation. Results. The serum IL-8 levels in group A were markedly increased, with pea ks at 3 hours after reperfusion, which was significantly higher than levels in group B (P <.01). In group A the arterial ketone body ratio, which refl ects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However in group B it decreased during hepatectomy but rapidly recovered 5 minutes after, hepatectomy. There was a significant negative correlation be tween the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83 P <.001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A. Conclusions. We have shown that HILP resulted in a augmented IL-8 release b ut not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the h epatic mitochondrial redox state. These findings suggest that IL-8 producti on may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for. hepat ic ischemia reperfusion injury but also for metastatic liver tumors.