Interactions of Immunopathological Mediators (Tumor Necrosis Factor-α, TGF-β, Prostaglandin E2) in Traumatized Individuals
Characterization of monokine action in septic shock is complicated by the interactive nature of the cytokines and the unusual activation status of the posttrauma macrophage-monocytes (MØ). The response of preseptic trauma patients’ MØ to bacterial stimuli is exaggerated when compared to normals’ MØ [1, 2]. MØ from trauma patients not only produce elevated tumor necrosis factor-α (TNF-α) levels, but the TNF-α which patients’ MØ produce is primarily cell-associated rather than secreted TNF-α as produced by normals’ MØ [1, 3, 4]. The trauma patients’ MØ TNF-α is often resistant to prostaglandin E2 (PGE2) downregulation . One hypothesis explaining this posttrauma aberrant monokine function is that the microenvironment around trauma patients’ MØ consists of high concentrations of secondary inducers of monokines (for example, substance P, immunoglobulin monomers, and complement split products), as well as elevated cytokines. It is the concomitant presence of these trauma-induced mediators during subsequent MØ induction that results in deranged monocyte responses, such as exaggerated production of some monokines and depression of both MØ antigen-presenting function and MØ plasmin-ogen-activator production. Some examples of altered cytokine response capacities of trauma patients’ MØ versus normals’ MØ are given in this section, and the implication for prophylactic therapy is discussed.
KeywordsTrauma Patient PGE2 Level Lipoxygenase Inhibitor Muramyl Dipeptide Nordihydroguaiaretic Acid
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