Update on the mechanisms of immune suppression of injury and immune modulation.
Major trauma results in massive impairment of immunologic reactivity, the clinical consequence of which consists in the high susceptibility of the traumatized individual toward serious infection. Whereas parts of the immune system are stimulated within a systemic, nondiscriminant, excessive whole-body inflammation, other functions within the complex of cell-mediated immunity (CMI) are dramatically paralyzed. Immune abnormalities in the aftermath of trauma occur in a sequence of states of cellular activation and within a complex order of events that is not yet well understood. Traumatic stress is causing disintegration of the intact monocyte (Mphi)-T cell interaction, which is associated with profound changes in Mphi forward-regulatory capacities and substantial depression of T cell function. Extensive tissue destruction results in the generation of numerous stimuli, such as phagocytosis, immune complexes, complement split products, and endo- and exotoxins, all of which contribute to excessive Mphi activation. Mphi then rapidly produce and release prostaglandin E2 (PGE2), a powerful endogenous immune suppressant. PGE2 is an inhibitor of T cell mitogenesis, interleukin 2 (IL-2) production, and IL-2 receptor expression; and it has a massive impact on the quality of B cell antibody synthesis. Most importantly, PGE2 represents an important cofactor for the induction of T-helper lymphocyte (TH) activity toward the TH2 direction. TH2 cells are associated with the synthesis of immunosuppressive cytokines, such as IL-4 and IL-10. Although immunosuppressive substrates are inhibitory for TH1 cells-the functional carriers of CMI-they support TH2 activity, which predisposes the host to develop infection. The endogenous ability of the organism to survive overwhelming trauma is insufficient and requires major exogenous support. Immune modulatory interventions, depending on the immune abnormalities seen in the traumatized host, should be started as early as possible after trauma in a preventive fashion to protect against organ tissue destruction. Ideally, it should protect all cellular host defense compartments from hyperactivation as well as from exhaustion. We do believe that only a combination of drugs can effectively control the posttraumatic dyshomeostasis of the various cell systems.
Faist
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E
Department of Surgery, Ludwig-Maximilians University, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany.
Schinkel
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C
Zimmer
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S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D018836:Inflammation Mediators / Q000502:physiology; D008262:Macrophage Activation / Q000276:immunology; D009102:Multiple Organ Failure / Q000276:immunology* / Q000628:therapy; D009104:Multiple Trauma / Q000276:immunology* / Q000628:therapy; D010587:Phagocytosis / Q000276:immunology; D011379:Prognosis; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000628:therapy
D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators