Interferon-γ increases monocyte HLA-DR expression without effects on glucose and fat metabolism in postoperative patients

Abstract

Tissue injury is associated with decreased cellular immunity and enhanced metabolism. Immunodepression is thought to be counteracted by interferon (IFN)-γ, which increases human leukocyte antigen (HLA)-DR expression. Hypermetabolism could be enhanced by IFN-γ because cytokines induce a hypermetabolic response to stress. In healthy humans, IFN-γ enhanced HLA-DR expression without effects on glucose and fat metabolism. In the present study, we evaluated whether IFN-γ lacks potential harmful side effects on metabolic and endocrine pathways while maintaining its beneficial effects on the immune system under conditions in which the inflammatory response system is activated. In 13 patients scheduled for major surgery, we studied HLA-DR expression on peripheral blood monocytes before surgery and postoperatively randomized the patients into an intervention and a placebo group. Subsequently, we evaluated the effects of a single dose of IFN-γ vs. saline on short-term monocyte activation, glucose and lipid metabolism, and glucose and lipid regulatory hormones. HLA-DR expression on monocytes was restored from postoperative levels of 54% (42-60%; median and interquartiles) to 92% (91-96%) 24 h after IFN-γ adminstration but stayed low in the placebo-treated patients. IFN-γ did not affect glucose metabolism (plasma glucose, rate of appearance and dissappearance of glucose) and lipid metabolism (plasma glycerol, plasma free fatty acids, and rates of appearance and disappearance of glycerol). IFN-γ had no effect on plasma cortisol, adrenocorticotropic hormone, growth hormone, insulin, C-peptide, glucagon, epinephrine, and norepinephrine concentrations. We conclude that IFN-γ exerts a favorable effect on cell-mediated immunity in patients after major surgery without effects on glucose and lipid metabolism.