Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans

To evaluate whether interferon-gamma (IFN-gamma) is involved in the interac tion between the immune and endocrine systems in vivo, we studied six healt hy subjects twice in a placebo-controlled trial: once after administration of recombinant human IFN-gamma and, on another occasion, after administrati on of saline. The rate of appearance of glucose was determined by infusion of [6,6-H-2(2)]glucose and resting energy expenditure by indirect calorimet ry. Human leukocyte antigen-DR gene expression on monocytes and serum neopt erin increased after administration of IFN-gamma (P < 0.05 vs. control). IF N-gamma increased serum interleukin-6 levels significantly. Levels of tumor necrosis factor-cr, remained below detection limits. IFN-gamma increased p lasma concentrations of ACTH and cortisol (P < 0.05 vs. control), IFN-gamma did not alter concentrations of growth hormone, (nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth factor I. IFN-gamma did not al ter plasma concentrations of glucose and free fatty acids nor the rate of a ppearance of glucose. IFN-I, increased resting energy expenditure significa ntly. We conclude that IFN-gamma is a minor stimulator of the endocrine and metabolic pathways. Therefore, IFN-gamma by itself is probably not a major mediator in the interaction between the immune and the endocrine and metab olic systems.