IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans
Tóm tắt
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.
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Tài liệu tham khảo
Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, and Hainque B.Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss.J Clin Endocrinol Metab85: 3338–3342, 2000.
Dickensheets HL, Freeman SL, Smith MF, and Donnelly RP.Interleukin-10 upregulates tumor necrosis factor receptor type-II (p75) gene expression in endotoxin-stimulated human monocytes.Blood90: 4162–4171, 1997.
Dinarello CA.Induction of interleukin-1 and interleukin-1 receptor antagonist.Semin Oncol24: S9, 1997.
Heuertz RM, Piquette CA, and Webster RO.Rabbits with elevated serum C-reactive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a-induced alveolitis.Am J Pathol142: 319–328, 1993.
Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, and Yano Y.Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus.J Clin Endocrinol Metab83: 859–862, 1998.
Matthys P, Mitera T, Heremans H, Van Damme J, and Billiau A.Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release ind-galactosamine-sensitized and unsensitized mice.Infect Immun63: 1158–1164, 1995.
Ridker PM, Rifai N, Stampfer MJ, and Hennekens CH.Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.Circulation17, 2000.
Tilg H, Trehu E, Atkins MB, Dinarello CA, and Mier JW.Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.Blood83: 113–118, 1994.