Robert S. Pekarek

The Effect of Leukocytic Endogenous Mediator (LEM) on the Tissue Distribution of Zinc and Iron

Summary Leukocytic endogenous mediator (LEM) was shown to induce significant alterations in zinc and iron metabolism. Isotopic studies, employing 65Zn and 59Fe demonstrated that LEM stimulated a rapid redistribution of zinc and iron within the tissues of the host, with a significant uptake of these two metals by the liver.

Characterization of the endogenous mediator(s) of serum zinc and iron depression during infection and other stresses.

Summary Serum zinc and iron concentrations were shown to be decreased significantly by a common heat labile endogenous mediator present in the serum of animals within 2 hr after the administration of a variety of inflammation inducing agents. The endogenous mediator obtained from PMN leukocytes of peritoneal exudates produced significant dose-dependent reductions in both serum zinc and iron concentrations. Preliminary data characterize the mediator as a heat labile, nondialyzable, low molecular weight protein (10,000-30,000 mol wt).

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.

ACUTE STRESS AND TRACE ELEMENT METABOLISM

Publisher Summary This chapter discusses acute stress and trace element metabolism. While considering the effect of acute stress upon the metabolism of a trace element, one must consider the fundamental physiological role of the element, methods available for its analysis, and the status of general and specific trace-metal nutrition in the host. Within cells, magnesium is related functionally to the activity of enzyme systems, especially those that generate high-energy phosphate bonds and control mitochondrial oxidative phosphorylation. Magnesium is a necessary cofactor of DNA, RNA, and ribosomes. It is needed for the binding of mRNA to polysomal subunits and for the activation of aminoacyl-sRNA complexes during protein synthesis. The extracellular concentration of magnesium ions influences both the nerve-cell conduction and myoneural junction activity. Excessive magnesium ions can produce local or general anesthesia, asystole, and curare-like paralysis. Deficiency of magnesium produces a syndrome of central nervous system irritability. The primary functional role of iron is oxygen transport via hemoglobin. Iron further serves as an essential cofactor for a number of heme and non-heme metalloenzymes that are important for oxygen and hydrogen exchange or electron transport. Iron also plays a role in maintaining the structure and integrity of polyribosomes and is important in protein synthesis. Zinc is an integral constituent and cofactor of more than twenty metalloenzymes. Because of relatively high concentrations of zinc found in various endocrine glands, this element may influence the secretion of several hormones. The important role of zinc in promoting the healing of thermal and surgical wounds adds further support to this hypothesis.

Relationship between serum chromium concentrations and glucose utilization in normal and infected subjects.

Studies in healthy individuals demonstrate that serum chromium concentrations fall precipitously following the intravenous administration of a 30-gm. glucose load. Significant decreases from baseline control fasting serum Cr concentrations were also observed when intravenous glucose was given during sandfly fever. Glucose disappearance rates also decreased significantly to approximately one half of pre-illness control values while serum Cr values declined still further. In addition, serum Cr disappearance rates could be calculated. When individual preexposure and postexposure serum glucose and Cr disappearance rates were compared, a significant linear correlation was found (P <0.05). Acute infection appears to reduce the availability of circulating Cr, which may contribute to the altered glucose metabolism characteristic of acute infections even in the presence of elevated insulin levels and other hormonal changes.

Changes in individual plasma amino acids following experimentally induced sand fly fever virus infection

Abstract Fasting concentrations of 21 individual plasma amino acids were determined in daily (7:30 a.m.) serial samples from eight volunteers infected with sand fly fever virus and compared to values obtained in six separate daily preexposure baseline measurements in each volunteer, as well as to serial measurements in three unexposed control subjects. By 47 hr after inoculation and before the onset of fever or other clinical indications of infection, most individual plasma amino acids were significantly depressed below preexposure values. These changes began before the marked decrement in protein intake during the illness. Such changes in plasma amino acids did not occur in control subjects. Reduction in amino acid concentrations persisted until after the lysis of fever and did not coincide in timing with alterations in white blood counts or serum Zn and Fe values. Urinary total nitrogen, urea, and alpha amino nitrogen were not altered during the course of sand fly fever in these subjects. Although food intake was reduced during sand fly fever, the magnitude of the amino acid depression was far greater than that reported during starvation or protein deprivation in non-infected subjects, and the sequence of changes in plasma valine, alanine, and glycine followed patterns different from those reported during starvation. It may be postulated that unusually large quantities of certain plasma amino acids were taken up by the cells of the liver and other visceral tissues during this infection. Plasma phenylalanine responded in a manner different from that of the other amino acids. It was decreased on day 2 after exposure to the virus but by day 4 and 5 was significantly increased above preinfection values. This resulted in a significant increase in the phenylalaninetyrosine ratio during the febrile phase of sand fly fever.

Mediator of Hepatic Amino Acid Flux in Infected Rats

Summary Live D. pneumoniae, but not endotoxin or double-stranded polynucleotides, stimulated a flux of cycloleucine into liver. Sterile, 2-hr serum from D. pneumoniae-infected rats and secretions obtained from rat peritoneal leukocytes can also mediate a flux of cycloleucine into liver of normal recipient rats. The data were interpreted as evidence that one or more proteins synthesized and excreted by leukocytes can act as humoral intermediates in the stimulation of amino acid flux into liver tissue.

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.

The direct determination of serum chromium by an atomic absorption spectrophotometer with a heated graphite atomizer.

Abstract By the use of a heated graphite atomizer, serum chromium concentrations can now be measured directly by atomic absorption spectrophotometry in 50-μl serum samples. Pretreatment or tedious extraction procedures of serum samples are avoided by this relatively simple, rapid, and reproducible method. Interference by other metals or salts in serum can be eliminated by this technique of selective volatilization. The coefficient of variability on a single pooled serum sample was 5.8%, and a value of 100.6% was obtained in recovery studies. When serum Cr concentrations were measured in a group of 15 healthy young adults, a mean serum concentration of 1.58 ppb (± SE of 0.08) was obtained. The results obtained can be attributed to the sensitivity of the analytical system, the reduction of possible sources of exogenous contamination, and the elimination of interference by other elements within the sample or system.

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.