Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury

The mechanism of immunodepression after brain injury is not yet clear. Here we demonstrate rapid systemic release of the immunoinhibitory cytokine interleukin-10, monocytic deactivation and a high incidence of infection in patients with 'sympathetic storm' due to acute accidental or iatrogenic brain trauma. In vitro studies showed that within minutes catecholamines trigger the secretion of interleukin-10 from unstimulated monocytes through a -adrenoreceptor-mediated, cAMP/protein kinase A-dependent pathway. We found that in a rat model of acute brain injury, the receptor antagonist propranolol prevented the increase of interleukin-10 plasma levels. Rapid monocytic interleukin-10 release after sympathetic activation may represent a common pathway for immunodepression induced by stress and injury.

1. Rodriguez, J.L. et al. Pneumonia: incidence, risk factors, and outcome in injured patients. I. Trauma. 31, 907−912 (1991). | ChemPort |
2. Hsieh, A.H., Bishop, M.J., Kubilis, P.S., Newell, D.W. & Pierson, D.J. Pneumonia following closed head injury. Am. Rev. Respir. Dis. 146, 290−294 (1992). | PubMed  | ISI | ChemPort |
3. Jarek, M.J., Legare, E.J., McDermott, M.T., Merenich, J.A. & Kollef, M.H. Endocrine profiles for outcome prediction from the intensive care unit. Crit. Care Med. 21, 543−550 (1993). | PubMed  | ISI | ChemPort |
4. Chiolero, R. & Berger, M. Endocrine response to brain injury. New Horiz. 2, 432−442 (1994). | PubMed  | ChemPort |
5. Rothwell, P.M. & Lawler, P.G. Prediction of outcome in intensive care patients using endocrine parameters [see comments]. Crit. Care Med. 23, 78−83 (1995). | Article | PubMed  | ISI | ChemPort |
6. Kapcala, L.P., Chautard, T. & Eskay, R.L. The protective role of the hypothalamic-pituitary-adrenal axis against lethality produced by immune, infectious, and inflammatory stress. Ann. NY Acad. Sci. 771, 419−437 (1995). | PubMed  | ChemPort |
7. Adcock, I.M. et al. Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. Am. J. Physiol. 268, C331−8 (1995). | PubMed  | ISI | ChemPort |
8. Sternberg, E.M. Neuroendocrine factors in susceptibility to inflammatory disease: focus on the hypothalamic-pituitary-adrenal axis. Horm. Res. 43, 159−161 (1995). | PubMed  | ISI | ChemPort |
9. Koff, W.C. Fann, A.V., Dunegan, M. A.& Lachman, L. B. Catecholamine-induced suppression of interleukin-1 production. Lymphokine Res. 5, 239−247 (1986). | PubMed  | ISI | ChemPort |
10. 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. 97, 713−719 (1996). | PubMed  | ChemPort |
11. Elenkov, I.J., Papanicolaou, D. A., Wilder, R. L. & Chrousos, G. P. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc. Assoc. Am. Physicians. 108, 374−381 (1996). | PubMed  | ISI | ChemPort |
12. Gibbons, R. A., Martinez, O. M., Lim, R. C., Horn, J. K. & Garovoy, M. R. Reduction in HLA-DR, HLA-DQ and HLA-DP expression by Leu-M3+ cells from the peripheral blood of patients with thermal injury. Clin. Exp. Immunol. 75, 371−375 (1989). | PubMed  | ISI | ChemPort |
13. Guillou, P. J. Biological variation in the development of sepsis after surgery or trauma. Lancet 342, 217−220 (1993). | Article | PubMed  | ISI | ChemPort |
14. Livingston, D. H., Appel, S. H., Wellhausen, S. R., Sonnenfeld, G. & Polk, H. C. Jr. Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch. Surg. 123, 1309−1312 (1988).
15. Asadullah, K. et al. Very low monocytic HLA-DR expression indicates high risk of infection - Immunomonitoring for patients after neurosurgery and patients during high dose steroid therapy. Eur. J. Emergency Med. 2, 184−190 (1995). | ChemPort |
16. Döcke, W. D. et al. in 4th International Congress on The Immune Consequences of Trauma, Shock and Sepsis - Mechanisms and Therapeutic Approaches. (eds. Faist, E., Baue, A.E. & Schildberg, F.W.) 293−298 (Monduzzi Editore, Bologna, ltaly, 1997).
17. Volk, H. D. et al. Diagnostic value of an immune monitoring program for the clinical management of immunosuppressed patients with septic complications. Clin. Transplant. 3, 246−252 (1989). | ISI |
18. Volk, H. D. et al. Monocyte deactivation - rationale for a new therapeutic strategy in sepsis. Intensive. Care Med. 22 Suppl 4, S474−81 (1996).
19. Döcke, W. D. et al. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nature Med 3, 678−681 (1997). | Article | PubMed  | ISI | ChemPort |
20. Randow, F. et al. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J. Exp. Med. 181, 1887−1892 (1995). | Article | PubMed  | ISI | ChemPort |
21. Moore, K. W., O'Garra, A., de Waal Malefyt, R., Vieira, P. & Mosmann, T. R. Interleukin-10. Annu. Rev. Immunol. 11, 165−190 (1993). | Article | PubMed  | ISI | ChemPort |
22. Asadullah, K. et al. Immunodepression following neurosurgical procedures. Crit. Care Med. 23, 1976−1983 (1995). | Article | PubMed  | ISI | ChemPort |
23. Bone, R. C. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit. Care Med. 24, 1125−1128 (1996). | Article | PubMed  | ISI | ChemPort |
24. Platzer, C., Meisel, C. Vogt, K., Platzer, M. & Volk, H. D. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and CAMP elevating drugs. Int. Immunol. 7, 517−523 (1995). | PubMed  | ISI | ChemPort |
25. Wanidworanun, C. & Strober, W. Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J. Immunol. 151, 6853−6861 (1993). | PubMed  | ISI | ChemPort |
26. Dinarello, C. A. & Thompson, R. C. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol. Today 12, 404−410 (1991). | Article | PubMed  | ISI | ChemPort |
27. Heesen, M. et al. Increase of interleukin-6 plasma levels after elective craniotomy: influence of interleukin-10 and catecholamines. Acta Neurochir. Wien. 138, 77−80 (1996). | PubMed  | ChemPort |
28. Suberville, S. et al. Regulation of interleukin-10 production by beta-adrenergic agonists. Eur. I. Immunol. 26, 2601−2605 (1996). | ChemPort |
29. Uottla, P. The role of cyclic AMP and oxygen intermediates in the inhibition of cellular immunity in cancer. Cancer Immunol. Immunother. 43, 1 −9 (1996). | PubMed  | ISI | ChemPort |
30. Szabo, C. et al. Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. Immunology 90, 95−100 (1997). | Article | PubMed  | ISI | ChemPort |
31. Karlsberg, R. P., Cryer, P. E. & Roberts, R. Serial plasma catecholamine response early in the course of clinical acute myocardial infarction: relationship to infarct extent and mortality. Am. Heart J. 102, 24−29 (1981). | Article | PubMed  | ISI | ChemPort |
32. Döcke, W. D. et al. Rapid IL-10 release and signs for immunodepression after acute myocardial infarction. Crit. Care Med. 25, A50 (Abstract) (1997). | ISI |
33. Hahn, P. Y. et al. Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 4, 269−273 (1995). | PubMed  | ISI | ChemPort |
34. Naito, Y. et al. Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery. Anesthesiology 77, 426−431 (1992). | PubMed  | ISI | ChemPort |
35. Fabian, T. C. et al. Reduced tumor necrosis factor production in endotoxin-spiked whole blood after trauma: experimental results and clinical correlation. Surgery 118, 63−72 (1995). | PubMed  | ISI | ChemPort |
36. Sherry, R. M., Cue, J. I., Goddard, J. K., Parramore, J. B. & DiPiro, J. T. Interleukin-10 is associated with the development of sepsis in trauma patients. J. Trauma. 40, 613−616 (1996). | PubMed  | ISI | ChemPort |
37. Dunn, A. J. Infection as a stressor: a cytokine-mediated activation of the hypothal-amopituitary-adrenal axis? Ciba. Found. Symp. 172, 226−239 (1993). | PubMed  | ISI | ChemPort |
38. Cheng, G. J., Morrow Tesch, J. L., Beller, D. I., Levy, E. M. & Black, P. H. Immunosuppression in mice induced by cold water stress. Brain Behav. Immun. 4, 278−291 (1990). | PubMed  | ChemPort |
39. Zwilling, B. S., Brown, D., Feng, N., Sheridan, J. & Pearl, D. The effect of adrenalectomy on the restraint stress induced suppression of MHC class II expression by murine peritoneal macrophages. Brain Behav. lmmun. 7, 29−35 (1993). | Article | ChemPort |
40. Dobbin, J. P., Harth, M., McCain, G. A., Martin, R. A. & Cousin, K. Cytokine production and lymphocyte transformation during stress. Brain Behav. Immun. 5, 339−348 (1991). | Article | PubMed  | ISI | ChemPort |
41. Zorrilla, E. P., Redei, E. & DeRubeis, R. J. Reduced cytokine levels and T-cell function in healthy males: relation to individual differences in subclinical anxiety. Brain Behav. lmmun. 8, 293−312 (1994). | Article | ChemPort |
42. justice, B. Critical life events and the onset of illness. Compr. Ther. 20, 232−238 (1994). | PubMed  | ChemPort |

	Top

	Top