Abstract
To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated with LPS in the presence or absence of these stress hormones. Epinephrine caused a dose-dependent increase in LPS-induced IL-8 production, which was mediated exclusively via beta-adrenergic receptors, as reflected by the facts that beta (but not alpha) receptor blockade reversed the epinephrine effect and beta (but not alpha) receptor stimulation reproduced the epinephrine effect. Further, elevating cellular cyclic AMP (cAMP) concentrations, a known effect of beta-adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced IL-8 production. Epinephrine-induced upregulation of IL-10 production masked an even more pronounced stimulating effect of this hormone on IL-8 synthesis, as indicated by the finding that the extent of IL-8 upregulation was greater in the presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose-dependently inhibited LPS-induced IL-8 production and reversed epinephrine-induced enhancement of IL-8 production. Epinephrine and hydrocortisone have opposite effects on IL-8 production, which may be relevant for the understanding of endogenous and therapeutic stress hormone influences on IL-8 mediated inflammation.
Full Text
The Full Text of this article is available as a PDF (163.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
- Chollet-Martin S., Montravers P., Gibert C., Elbim C., Desmonts J. M., Fagon J. Y., Gougerot-Pocidalo M. A. High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome. Infect Immun. 1993 Nov;61(11):4553–4559. doi: 10.1128/iai.61.11.4553-4559.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
- DeForge L. E., Kenney J. S., Jones M. L., Warren J. S., Remick D. G. Biphasic production of IL-8 in lipopolysaccharide (LPS)-stimulated human whole blood. Separation of LPS- and cytokine-stimulated components using anti-tumor necrosis factor and anti-IL-1 antibodies. J Immunol. 1992 Apr 1;148(7):2133–2141. [PubMed] [Google Scholar]
- DeForge L. E., Tracey D. E., Kenney J. S., Remick D. G. Interleukin-1 receptor antagonist protein inhibits interleukin-8 expression in lipopolysaccharide-stimulated human whole blood. Am J Pathol. 1992 May;140(5):1045–1054. [PMC free article] [PubMed] [Google Scholar]
- Donnelly S. C., Strieter R. M., Reid P. T., Kunkel S. L., Burdick M. D., Armstrong I., Mackenzie A., Haslett C. The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med. 1996 Aug 1;125(3):191–196. doi: 10.7326/0003-4819-125-3-199608010-00005. [DOI] [PubMed] [Google Scholar]
- Hack C. E., Hart M., van Schijndel R. J., Eerenberg A. J., Nuijens J. H., Thijs L. G., Aarden L. A. Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun. 1992 Jul;60(7):2835–2842. doi: 10.1128/iai.60.7.2835-2842.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
- Hechtman D. H., Cybulsky M. I., Fuchs H. J., Baker J. B., Gimbrone M. A., Jr Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol. 1991 Aug 1;147(3):883–892. [PubMed] [Google Scholar]
- Mukaida N., Shiroo M., Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366–1371. [PubMed] [Google Scholar]
- Severn A., Rapson N. T., Hunter C. A., Liew F. Y. Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol. 1992 Jun 1;148(11):3441–3445. [PubMed] [Google Scholar]
- Standiford T. J., Kunkel S. L., Rolfe M. W., Evanoff H. L., Allen R. M., Strieter R. M. Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone. Am J Respir Cell Mol Biol. 1992 Jan;6(1):75–81. doi: 10.1165/ajrcmb/6.1.75. [DOI] [PubMed] [Google Scholar]
- Strieter R. M., Koch A. E., Antony V. B., Fick R. B., Jr, Standiford T. J., Kunkel S. L. The immunopathology of chemotactic cytokines: the role of interleukin-8 and monocyte chemoattractant protein-1. J Lab Clin Med. 1994 Feb;123(2):183–197. [PubMed] [Google Scholar]
- Van Zee K. J., DeForge L. E., Fischer E., Marano M. A., Kenney J. S., Remick D. G., Lowry S. F., Moldawer L. L. IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol. 1991 May 15;146(10):3478–3482. [PubMed] [Google Scholar]
- Verghese M. W., Snyderman R. Hormonal activation of adenylate cyclase in macrophage membranes is regulated by guanine nucleotides. J Immunol. 1983 Feb;130(2):869–873. [PubMed] [Google Scholar]
- de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Waal Malefyt R., Figdor C. G., Huijbens R., Mohan-Peterson S., Bennett B., Culpepper J., Dang W., Zurawski G., de Vries J. E. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol. 1993 Dec 1;151(11):6370–6381. [PubMed] [Google Scholar]
- van der Poll T., Barber A. E., Coyle S. M., Lowry S. F. Hypercortisolemia increases plasma interleukin-10 concentrations during human endotoxemia--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3604–3606. doi: 10.1210/jcem.81.10.8855809. [DOI] [PubMed] [Google Scholar]
- van der Poll T., Coyle S. M., Barbosa K., Braxton C. C., Lowry S. F. Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest. 1996 Feb 1;97(3):713–719. doi: 10.1172/JCI118469. [DOI] [PMC free article] [PubMed] [Google Scholar]