Type-2 dominant cytokine gene expression following hepatic surgery

Abstract

Hemorrhage and ischemic liver injuries associated with hepatic resection are thought to play a role in postoperative complications, possibly through altered cytokine production. The current study was performed to investigate the effects of hepatectomy on cytokine gene expression. We collected blood preoperatively, at completion of operation, and on postoperative days 1 and 5 from ten patients undergoing hepatic resection. The peripheral blood mononuclear cells were evaluated with real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression of interleukin-10 (IL-10), proinflammatory cytokines (interferon-gamma [IFNgamma], IL-15, tumor necrosis factor alpha [TNFalpha], and chemokines regulated on activation, normal T expressed and secreted [RANTES], macrophage inflammatory protein 1 alpha [MIP-1alpha], [MIP-1beta]). Wilcoxon Rank and paired t-tests were used for statistical analysis. Immediately following hepatectomy there was a significant (31.4 +/- 60.5-fold; P < 0.05) increase in IL-10 gene expression that was sustained until the first postoperative day. In contrast, there was a significant downregulation (38 +/- 71 eight fold lower than preoperative; P < 0.05) of IFNgamma gene expression on day 1. By postoperative day 5, the changes in gene transcript levels of both IL-10 and IFNgamma had returned to the preoperative baselines. This contrasting change in IL-10 and IFNgamma gene expression in response to hepatic resection was statistically significant (P = 0.02). Hepatectomy elicits an imbalance towards the immunosuppressive type-2 cytokine profile in the early postoperative period. Measurement of cytokine gene transcripts following hepatic resection may have predictive value for clinical outcome, and deserves further study.