• Michael D Menger and Brigitte Vollmar.
• Institute for Clinical and Experimental Surgery, University of Saarland, 66421 Homburg-Saar, Germany. exmdme@uniklinik-saarland.de
• Langenbecks Arch Surg. 2004 Nov 1;389(6):475-84.

BackgroundExperimental and clinical studies have brought evidence that surgical trauma markedly affects the immune system, including both the specific and the non-specific immune response.Materials And MethodsThis report reviews the present knowledge on the mechanisms of surgical trauma-induced immune dysfunction and outlines experimental and clinical approaches to find effective treatment strategies.ResultsMajor surgical trauma induces an early hyperinflammatory response, which is characterized by (1) pro-inflammatory tumour necrosis factor alpha (TNF), interleukin (IL)-1, and IL-6 cytokine release and (2) neutrophil activation and microvascular adherence, as well as (3) uncontrolled polymorphonuclear (PMN) and macrophage oxidative burst. The massive and continuous IL-6 release induces an acute phase response, but, more importantly, also accounts for the up-regulation of major anti-inflammatory mediators, such as prostaglandin (PG) E2, IL-10 and transforming growth factor (TGF)-ss. This results in surgical, trauma-induced, immunosuppression, as indicated by (1) monocyte deactivation, reflected by the lack of monocytic TNF- production upon lipopolysaccharide (LPS) stimulation, and (2) a shift of the Th1/Th2 ratio towards a Th2-dominated cytokine pattern. The imbalance between pro-inflammatory and anti-inflammatory cytokines and immuno-competent cells determines the phenotype of disease and should help the physician to compose the therapeutic strategy. In fact, recent clinical studies have shown that both the initial uncontrolled hyperinflammation and the continued cell-mediated immunosuppression represent primary targets to counteract post-surgery immune dysfunction. The balance between inflammatory and anti-inflammatory forces may be restored by interferon gamma (IFN-gamma) to counteract monocyte deactivation; the anti-inflammatory PGE2 may be inhibited by indomethacin to attenuate immunosuppression; or the initial hyperinflammation may be targeted by administration of anti-inflammatory substances, such as granulocyte colony-stimulating factor (G-CSF), hydoxyethyl starch, or pentoxifylline.ConclusionsWhen drawing up the therapeutic regimen the physician should not consider hyperinflammation versus immunosuppression, but hyperinflammation and immunosuppression, aiming at restoring an appropriate mediator- and immune cell-associated balance.

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