In vitro and in vivo actions of zinc ion affecting cellular substances which influence host metabolic responses to inflammation.
Glycogen-stimulated rabbit peritoneal exudate cells (polymorphonuclear leukocytes, PMN) produce prostaglandins (PG) and substances which induce alterations (mediators) in experimental animals characteristic of host metabolic responses to infection and other acute inflammatory stresses. The effect of Zn2+ on mediator production and PG synthesis was examined because: Zn homeostasis is perturbed during infection, Zn is known to regulate some cellular functions, and there appears to be an interrelationship between PG synthesis and mediator production. Using exudate cells, 2 mM Zn2+ caused complete inhibition of in vitro PG synthesis as assessed by conversion of [1-14C] arachidonic acid into PG. This concentration of Zn2+ also inhibited production of substances mediating plasma Zn depression, hepatic amino acid "uptake", fever, and neutrophil release from bone marrow. Conversely, Zn2+ did not inhibit in vivo metabolic responses to these mediators. Zn-pretreatment of rabbits or simultaneous injection of Zn2+ and crude PMN-derived pyrogenic activity resulted in prolongation of fever. It is suggested that this action of Zn2+ may be attributed to either stabilization of cyclic AMP through inhibition of phosphodiesterase or a Zn-mediator interaction which stabilizes crude endogenous pyrogen. The potential physiological significance of these results includes: possible potentiation of the host's defense mechanisms by Zn2+ and its utilization for prolongation of fever to determine its effect on potentially temperature-dependent host defense mechanisms.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D002478:Cells, Cultured; D005334:Fever / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011749:Pyrogens / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D011453:Prostaglandins; D011749:Pyrogens; D013806:Theophylline; D015032:Zinc