Michael C. Powanda

The Effect of Leukocytic Endogenous Mediator (LEM) on Serum Copper and Ceruloplasmin Concentrations in the Rat

Summary Leukocytic endogenous mediator (LEM) was shown to produce significant increases in serum Cu and ceruloplasmin concentrations in the rat within 12 hr after its administration. This increase coincided with an increase in the incorporation of 3H-leucine into total serum proteins which also was shown to be induced by LEM.

Further evidence that leukocytic endogenous mediator (LEM) is not endotoxin

Despite several similarities, the effects of leukocytic endogenous mediator (LEM), a small protein, were further differentiated from bacterial endotoxin, a complex lipopolysaccharide, on the basis of non-identical biological activities. When either substance was administered to normal rats, each produced significant depression in serum zinc and iron concentrations, as well as a flux of amino acids to the liver. However, only LEM produced these effects on host metabolism in rats made tolerant to endotoxin. The effects of LEM and endotoxin on the synthesis and/or release of acute phase serum glubulins were also compared. Endotoxin produced a significant increase in only the α2-macrofeto-protein of normal rats. By contrast, LEM produced significant increases in all the acute phase serum protein fractions measured in either normal or endotoxin-tolerant rats. The differences and relationships between LEM and endotoxin on host responses are discussed.

Differential effect of parenteral zinc on the course of various bacterial infections.

Summary Intraperitoneal pretreatment of rats with zinc, as zinc chloride, 1 hr prior to bacterial challenge with S. typhimurium, F. tularensis, or S. pneumoniae enhanced mortality incidence in S. typhimurium infection only. Unlike previous reports concerning lead and cadmium, zincs potentiation of lethality in an endotoxin-producing gram-negative infection does not appear to be attributable to heavy metal-induced increases in sensitivity to the toxic aspects of endotoxin. In contrast to the results obtained with S. typhimurium, single and multiple zinc treatments enhanced survival incidence during the early postinfection period in rats infected with F. tularensis or S. pneumoniae. These diverse observations can possibly be explained, in part, by zincs ability to modify certain aspects of the hosts defense mechanism such as leukocytosis, phagocytosis, and cell-mediated immunity as well as by zincs inhibition of bacterial proliferation.

Further Characterization and Species Specificity of Leukocytic Endogenous Mediator (LEM)1

Summary A degree of cross species susceptibility was observed on the effects of leukocytic endogenous mediator (LEM) on serum zinc depression and amino acid flux. LEM was shown to be protein in nature, and relatively stable under a wider range of pH and conditions of storage. Although LEM shares several chemical and physical characteristics with endogenous pyrogen (EP), some differences between the chemical properties and species specificity of these two mediators were noted.

Alterations in Plasma Copper, Zinc, Amino Acids, and Seromucoid during Rocky Mountain Spotted Fever in Guinea Pigs

Summary Guinea pigs inoculated with virulent Rickettsia rickettsii responded with a significant increase in plasma copper concentration within 1 day, preceding fever and detectable rickettsemia by 2 and 4 days, respectively. A decrease in serum zinc concentration coinciding with peak rickettsemia was detectable on Day 5. Evidence of altered host nitrogen metabolism during this illness included a doubling of plasma sero-mucoid concentration and a significant rise in the plasma phenylalanine/tyrosine ratio.

Protective Effect of Clofibrate Against S. pneumoniae Infection in Rats

Summary Clofibrate, nominally an anti-hyperlipemic agent, added to the diet for a week prior to the inoculation of rats with S. pneumoniae protected some of the rats from what would normally be a uniformly lethal infection. Plasma from clofibrate-treated rats was neither bactericidal nor bacteriostatic, yet drug-treated rats displayed significantly diminished incidence and extent of bacteremia. Clofibrate does not alter carbon clearance, thus it is unlikely that clofibrate affords protection through enhanced reticuloendothelial removal of microorganisms. The mechanism and implications of clofibrate protection remain to be determined.

Clofibrate-induced alterations in serum protein patterns.

Abstract Clofibrate when added to the diet at 0.05 to 1.25% (w/w) not only causes an apparently dose-dependent decrease in serum cholesterol of rats but also markedly affects the plasma protein pattern. An increase in albumin is detectable by cellulose acetate strip electrophoresis, acrylamide gel electrophoresis, and by extraction of albumin from plasma. Cellulose acetate strip electrophoresis reveals a decrease in the α 2 -globulin fraction, while acrylamide gel electrophoresis indicates that there are manifold changes. Extractable seromucoid concentration declined from 440 mg/100 ml to 150 mg/ml as the dose of clofibrate increased. A concentration decrease in plasma glucose was also observed. Part of the decrement in seromucoid at low drug levels may be related to lessened haptoglobin concentration. The trypsin inhibitory capacity of the plasma was significantly decreased in what appeared to be a dose-dependent fashion. The decrease in seromucoid is consistent with the reduction in bound fraction of ribosomal RNA. Another explanation would appear to be required to explain the rise in albumin.

Metabolic Sequelae of Respiratory Q Fever in the Guinea Pig.

Summary Guinea pigs infected with Coxiella burnetii administered in small particle aerosols provides a model for naturally acquired respiratory Q fever. Increases in plasma copper and seromucoid concentrations and in lysozyme activity along with a decrease in plasma zinc paralleled increases in body temperature, spleen and lung weights, and the development of lesions. Circumstantial evidence indicates that these metabolic alterations may be related to the interaction between pulmonary macrophages and the parasite. These metabolic sequelae thus may have prognostic value in that they appear related to the disease process and are less likely to be obscured than fever or rickettsemia.