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1The Copenhagen Muscle Research Centre and 2The Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark
Submitted 19 February 2003 ; accepted in final form 20 April 2003
The purpose of the present study was to test the hypothesis that a
transient increase in plasma IL-6 induces an anti-inflammatory environment in
humans. Therefore, young healthy volunteers received a low dose of recombinant
human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion
were 
140 pg/ml, corresponding to the levels obtained during strenuous
exercise. The infusion of rhIL-6 did not induce enhanced levels of the
proinflammatory cytokine TNF-
but enhanced the plasma levels of the two
anti-inflammatory cytokines IL-1 receptor agonist (IL-1ra) and IL-10 compared
with saline infusion. In addition, C-reactive protein increased 3 h
post-rhIL-6 infusion and was further elevated 16 h later compared with saline
infusion. rhIL-6 induced increased levels of plasma cortisol and,
consequently, an increase in circulating neutrophils and a decrease in the
lymphocyte number without effects on plasma epinephrine, body temperature,
mean arterial pressure, or heart rate. In conclusion, this study demonstrates
that physiological concentrations of IL-6 induce an anti-inflammatory rather
than an inflammatory response in humans and that IL-6, independently of
TNF-, enhances the levels not only of IL-1ra but also of IL-10.
Furthermore, IL-6 induces an increase in cortisol and, consequently, in
neutrocytosis and late lymphopenia to the same magnitude and with the same
kinetics as during exercise, suggesting that muscle-derived IL-6 has a central
role in exercise-induced leukocyte trafficking.
cytokines; C-reactive protein; tumor necrosis factor-; neutrophils and lymphocytes; interleukin-1 receptor agonist
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