IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans

TLDR

The study tested whether a transient rise in plasma IL‑6 induces an anti‑inflammatory milieu in humans. Young healthy volunteers received a 3‑hour low‑dose recombinant IL‑6 infusion that raised plasma IL‑6 to ~140 pg/ml, comparable to levels seen during strenuous exercise. The infusion elevated anti‑inflammatory cytokines IL‑1ra and IL‑10, increased CRP and cortisol, caused neutrophilia and lymphopenia, but did not raise TNF‑α, demonstrating that physiological IL‑6 promotes an anti‑inflammatory response similar to that of exercise.

Abstract

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-α 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-α, 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.