Interleukin 1-induced depression of iron and zinc: role of granulocytes and lactoferrin.
The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.
D000818:Animals; D002460:Cell Line; D004731:Endotoxins / Q000633:toxicity; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000302:isolation & purification / Q000494:pharmacology*; D007501:Iron / Q000097:blood*; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism*; D007782:Lactoglobulins / Q000378:metabolism*; D008297:Male; D051379:Mice; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000097:blood*
D004731:Endotoxins; D007375:Interleukin-1; D007782:Lactoglobulins; D007501:Iron; D007781:Lactoferrin; D015032:Zinc