IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans.
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 approximately 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-alpha 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-alpha, 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.
Steensberg
Adam
A
The Copenhagen Muscle Research Centre, Rigshospitalet 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. SBERG@rh.dk
Fischer
Christian P
CP
Keller
Charlotte
C
Møller
Kirsten
K
Pedersen
Bente Klarlund
BK
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D015444:Exercise / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000097:blood / Q000502:physiology*; D007700:Kinetics; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D009504:Neutrophils; D011994:Recombinant Proteins / Q000008:administration & dosage; D012795:Sialoglycoproteins / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; D006854:Hydrocortisone