Abstract

Leukocyte endogenous mediator is a low molecular-weight protein synthesized by circulating monocytes and fixed macrophages of the reticuloendothelial system. Exogenous administration of leukocyte endogenous mediator to a well-nourished animal stimulates both specific and nonspecific immune function and replicates the protein metabolic response to infection, characterized by fever and increased amino acid oxidation, skeletal protein degradation and synthesis of “acute-phase” proteins. Leukocyte endogenous mediator administration also affords protection against semilethal doses of bacteremia in the well-nourished animal. In the protein-depleted host, synthesis or release of leukocyte endogenous mediator in response to infection appears to be reduced and the attenuated metabolic response may be attributed, in part, to a deficit in its production. However, nutritional repletion of the malnourished patient results in restoration of the capacity to produce leukocyte endogenous mediator usually within three to seven days, if adequate dietary protein is provided. Since protein malnutrition is associated with increased incidence and severity of bacterial infections, we postulate that the reduced synthesis and/or release of leukocyte endogenous mediator in protein malnutrition is detrimental. In those critically-ill, malnourished patients who cannot endogenously synthesize leukocyte endogenous mediator, and for clinical reasons cannot be repleted rapidly or are already infected and/or undergoing operative stress, exogenous administration of leukocyte endogenous mediator should be considered along with nutritional support. Administration of this protein to a seriously-ill malnourished individual should produce a metabolic profile of fever, increased urinary nitrogen excretion and falls in serum albumin concentrations that are generally considered pathologic. However, administration of leukocyte endogenous mediator over short periods of time should also provide the anabolic impetus for the augmented synthesis of proteins beneficial to recovery. In most cases, these countervailing forces of anabolism and catabolism should be of benefit to the host if the response to infection and injury is viewed as a physiologic redistribution of endogenous nutrients to meet the more critical and immediate needs of the stressed patient.

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