Role of Biochemical Mediators in Clinical Nutrition and Surgical Metabolism

Abstract

Over the past several decades, research on the role of mediators in inflammation, immunity, repair processes, cell growth, and substrate metabolism have centered around the use of purified products of stimulated macrophages. With the current availability of recombinant mediators, the participation of individual monokines in cellular metabolism has been more clearly defined. Interactions among various mediators have been demonstrated, but their exact role in metabolism is currently under intense study. With the use of recombinant monokines, formal evidence for their participation in the acute phase response has been developed. Their use has also assisted in the reinterpretation of data gathered in older studies using purified preparations, which were almost certainly contaminated with several monokines. In this review we will try to give the reader insight into recent advances in the understanding of the role of cellular mediators in relation to nutrition and intermediary metabolism. With a clearer knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop rationales for their therapeutic use as modulators of substrate metabolism during critical illness.

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

“…Thus, a single dose of recombinant human TNF to rats resulted in increased muscle proteolysis ( 10), while rats given the cytokine on a chronic schedule lose total body protein at rates higher than pair-fed controls (7). TNF administration augmented the amino acid release from peripheral tissues in cancer patients (9), and muscle protein degradation was accelerated by TNF given at doses smaller than those required to produce hemodynamic changes (34). In vitro work also seems to implicate TNF in enhancing protein degradation ( 12), although evidence for its direct mediation of this effect remains elusive (1 1, 35, 36).…”

Effect of Major Hepatectomy on Glucose and Lactate Metabolism

“…The liver is also considered to play a key role in lactate clearance and utilization, and hence to participate in the regulation of plasma lactate concentrations. 23 Contemporary developments in surgical, anesthesia, and critical care medicine have enabled surgeons to safely per-…”

Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase.

“…Indeed, endotoxin-induced shock and death has been prevented by administering antibodies to TNF to experimental animals before endotoxin administration (25,26). IL-1 (27,28) and TNF (29)(30)(31)(32) have been implicated as causative agents of accelerated muscle protein catabolism in conditions such as sepsis and cachexia; other studies suggest that neither agent induces muscle protein degradation, which may be caused by a yet unidentified cytokine (33)(34)(35)(36).…”