Submitted on February 4, 2002
Accepted on May 29, 2003
Interferon-gamma increases monocyte HLA-DR expression without effects on glucose and fat metabolism in post-operative patients
Jesse de Metz1, Johannes A Romijn2, Erik Endert3, Mariette T Ackermans3, Gerrit Jan Weverling4, Olivier R Busch5, Laurence T de Wit5, Dirk J Gouma4, Ineke J ten Berge6, and Hans P Sauerwein1*
1 Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands
2 Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
3 Department of Clinical Chemistry, Laboratoy of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands
4 Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands
5 Division of Surgery, Academic Medical Center, Amsterdam, The Netherlands
6 Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands; Renal Transplant Unit, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands; Clinical Immunology Laboratory, Academic Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: h.p.sauerwein{at}amc.uva.nl.
Tissue injury is associated with decreased cellular immunity and enhanced metabolism. Immuno-depression is thought to be counteracted by interferon-gamma (IFN-
), which increases human leukocyte antigen-DR (HLA-DR) expression. Hypermetabolism could be enhanced by IFN-, since cytokines induce an hypermetabolic response to stress. In healthy humans IFN- enhances HLA-DR expression without effects on glucose and fat metabolism. In the present study we evaluated whether IFN- 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. We studied in thirteen patients scheduled for major surgery, HLA-DR expression on peripheral blood monocytes prior to surgery and post-operatively randomized the patients into an intervention and placebo group. Subsequently, we evaluated the effects of a single dose of IFN- 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 post-operative levels of 54%(42-60%) (median and interquartiles) to 92%(91-96%) 24 hours after IFN- adminstration, but stayed low in the placebo treated patients. IFN- did not effect glucose metabolism (plasma glucose, rate (R) of appearance (a) and dissappearance (d) of glucose) and lipid metabolism (plasma glycerol, plasma free fatty acids and Ra and Rd of glycerol). IFN- had no effect on plasma cortisol, adrenocorticotropic hormone, growth hormone, insulin, c-peptide, glucagon, epinephrine and norepinephrine concentrations. We conclude that IFN- exerts a favorable effect on cell-mediated immunity in patients after major surgery without effects on glucose and lipid metabolism.
