ENDOCRINE AND METABOLIC EFFECTS OF INTERFERON-ALPHA IN HUMANS

Interferon-alpha (IFN alpha) concentrations are increased in condition s associated with tissue injury. To investigate the endocrine and meta belie actions of IFN alpha in vivo, we studied eight healthy controls on two occasions, once after administration of 5 million units/m(2) r hIFN alpha and once after administration of saline (control). Rates of appearance (R(a)) of glucose and glycerol in plasma were measured by infusion of [3-H-3]glucose and D-5-glycerol, respectively. Energy expe nditure and substrate oxidation were determined by indirect calorimetr y. IFN alpha induced increases in plasma concentrations of norepinephr ine (225 +/- 93%; P < 0.02 vs. control), epinephrine (272 +/- 80%; P < 0.05), cortisol (353 +/- 63%; P < 0.02), glucagon (50 +/- 12%; P < 0. 05), free fatty acids (223 +/- 61%; P < 0.02), and glycerol (68 +/- 21 %; P < 0.02) and in resting energy expenditure (36 +/- 50%; P < 0.03). The R(a) of glycerol (169 +/- 39%; P < 0.02) and fat oxidation (104 /- 23%, P < 0.02) were also increased after IFN alpha treatment. The R (a) of glucose was higher at the end of the recombinant human IFN alph a treatment day than in the control experiment (12.83 +/- 1.08 vs. 9.3 4 +/- 0.46 mu mol/kg . min; P < 0.03). It is concluded that IFN alpha administration induces, directly or indirectly, major endocrine and me tabolic changes and is probably part of the cytokine network mediating the endocrine and catabolic reactions to tissue injury.