Masayuki Sho

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

BACKGROUNDnWe have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence 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 cytokines in the tumor response.nnnMETHODSnSixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringers lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation.nnnRESULTSnThe serum IL-8 levels in group A were markedly increased, with peaks 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 reflects 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 between 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.nnnCONCLUSIONSnWe have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.