Depressed response of plasma iron and zinc to endotoxin and LEM in STZ-diabetic rat.
Laboratory and epidemiological evidence indicate that the enhanced flux of iron and zinc from the plasma to the storage compartments, such as liver, serves as a protective host response to combat infection. Studies were performed to determine the status of this nonspecific immune response in the diabetic animal, since it is commonly held that the diabetic has an increased incidence and susceptibility to infection. Normal rats and rats previously rendered diabetic by streptozotocin (STZ) were injected with either saline or Escherichia coli endotoxin, and plasma levels of zinc, iron, and copper were monitored 8 hr thereafter. Diabetic rats reduced their plasma zinc and iron levels by 35 and 25%, respectively, in response to endotoxin injection whereas control rats had a 70% decrease in zinc and a 46% depression in iron. Insulin administration to the diabetic rats restored the ability to decrease plasma zinc and iron to the same degree as control rats. Plasma copper did not change in any group. Further investigation suggested that the defect in trace metal response occurred after the secretion of leukocytic endogenous mediator (LEM) in the inflammatory response pathway. It is concluded that STZ-diabetic rats have a diminished ability to decrease plasma zinc and iron in response to endotoxin, and that this defect is due to an ineffective response of target tissues to the effects of leukocytic endogenous mediator. Furthermore, it is postulated that the hyperinsulinemia associated with the stress of infection functions to lower plasma zinc and, possibly, iron, thereby allowing the host to better combat infection.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000276:immunology; D007375:Interleukin-1; D007501:Iron / Q000097:blood*; D008297:Male; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D012772:Shock, Septic / Q000097:blood*; D015032:Zinc / Q000097:blood*
D007375:Interleukin-1; D011506:Proteins; C008270:leukocyte endogenous mediator; D007501:Iron; D015032:Zinc