Showing papers by "Charles A. Dinarello published in 1978"

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

Abstract: The ability of highly purified human leukocytic pyrogen (LP) to induce neutrophil lysosomal protein release is described. Human peripheral blood neutrophils isolated by Ficoll-Hypaque and dextran sedimentation were exposed to purified human LP. The specific granule-associated proteins, lysozyme and lactoferrin were selectively released, whereas primary granule (beta-glucuronidase) and cytoplasmic (lactic dehydrogenase) enzyme markers were not. Optimum release was observed after 45 min in the presence of Ca++ and Mg++. Cytochalasin B (5 microgram/ml) had no effect on LP-induced lysosomal enzyme release. Since the pyrogenicity of LP is dependent on prostaglandin synthesis, the effect of two potent inhibitors of prostaglandin synthesis on lysozyme release was studied. Both indomethacin and naproxen failed to inhibit specific granule protein release. These observations suggest that the concommitance of fever, elevated serum or urine lysozyme and hypoferremia may, in part, be explained by the interaction of LP and peripheral blood neutrophils.

Pathogenesis of Fever in Man

Abstract: FOR centuries before the introduction of the thermometer, fever was a well recognized sign of disease. During the Age of Pericles (ca. 450 B.C.) physicians accurately described the physical findings associated with the fevers of typhoid and other infections. However, only during the past three decades has the mechanism by which disease causes a rise in body temperature begun to be clarified. Studies in animals and in human beings have expanded knowledge of the pathogenesis of fever, and, more recently, information has been obtained at the molecular level. This report reviews established concepts and presents newer information on the pathogenesis . . .

The pyrogenicity of the synthetic adjuvant muramyl dipeptide and two structural analogues.

Abstract: The pyrogenic efect of the synthetic adjuvant N-acetylmuramyl-L-alanine-D-isoglutamine, also known as muramyl dipeptide (MDP), was studied in rabbits. MDP induced biphasic fevers in rabbits, but two structural analogues, N-acetylmuramyl-L-alanine-D-glutamic acid (MDPA) and the dimethylester of MDPA, were 10 times less pyrogenic. This finding was supported by studies in which MDP and its analogues released leukocytic pyrogen (LP) from rabbit phagocytic cells in vitro. In addition, MDP released LP from human phagocytes. Human phagocytes, however, required a 10-fold greater concentration of MDP than did rabbit cells. The structural analogues were similarly less effective than the parent molecule in releasing LP from human cells. All preparations of MDP were negative in the limulus amebocyte lysate test and failed to show pyrogenic cross-tolerance with bacterial endotoxin. Thus MDP, which is a pyrogenic molecule, is also able to release LP from rabbit phagocytes and to a lesser degree from human phagocytes, but does not cause gelation of limulus amebocyte lysate.