Cytokines,Muscle Proteolysis,and the Catabolic Response to Infection and Inflammation

Abstract

Apart from fever, the most striking characteristic of infection to the layman and the professional alike are the development of anorexia and associated weight loss. Although the unintentional weight loss is composed of both fat and lean tissue, it is the loss of the lean tissue representing protein (nitrogen) that has the greatest clinical impact. The relationship among inflammation and infection, protein metabolism, and endogenous mediators has been both a general research interest for others and a personal one of this laboratory for some time.

Early studies demonstrated a catabolic nitrogen response to fever and infection (1, 2). Still other investigators reported that factors derived from white blood cells, which were at that time collectively termed leukocyte endogenous mediator (LEM), could be identified and postulated their role in these responses (3, 4). LEM was considered to be a group of low molecular weight, heat-labile proteins that were synthesized and released by circulating and fixed monocytes of the reticuloendothelial system in response to inflammation and infection (4, 5). In the study of the role of these factors in the protein metabolic response to inflammation and injury, initial work employed the amino acid analogs aminoisobutyric acid and 1-aminocyclopenta-necarboxylic acid to show a direct hepatic effect of LEM to take up, transport, and incorporate amino acids into protein, specifically acute phase globulin (6–8). Our initial experimental work with LEM and its effect on protein metabolism employed a relatively crude product produced by intraperitoneal injection of shellfish glycogen into rabbits and harvesting a cell-free supernatant (9).