Open Access

Catecholamine-induced interleukin-10 release: a key mechanism in systemic immunodepression after brain injury

  • Christian Woiciechowsky1,
  • Britta Schöning1,
  • Wolfgang R Lanksch1,
  • Hans-Dieter Volk2 and
  • Wolf-Dietrich Döcke2
Critical Care19993:R107

DOI: 10.1186/cc375

Received: 7 September 1999

Accepted: 17 September 1999

Published: 8 November 1999

Abstract

Background

Infections after severe brain injury or polytrauma are still a problem, and may be the result of a brain-mediated disturbed systemic immunoreactivity. The mechanism that connects initial brain affection and systemic immunodepression, however, is still poorly understood.

Review

In order to analyze the influence of the sympathetic nervous system in the context of brain injury on systemic immune functions, we performed various in vitro, in vivo and clinical studies. We were able to demonstrate that catecholamines trigger the release of the strong anti-inflammatory cytokine interleukin (IL)-10 from peripheral blood mononuclear cells and monocytes. In animal models we were able to show that increased intracranial pressure as well as intracerebral proinflammatory cytokines (eg IL-1β) produce a rapid systemic IL-10 release through sympathetic activation. Thus, in both models, the predominant role of catecholamines for this effect was confirmed by the complete prevention of IL-10 increase after β-adrenoreceptor blockade. Moreover, in clinical studies we clearly demonstrated that neurosurgical procedures involving brain-stem manipulation invoke sympathetic activation and a rapid systemic IL-10 release. Remarkably, this was associated with monocytic deactivation – a sign of systemic immunodepression and a high risk of infectious complications.Finally, these data were validated in patients with accidental brain injury, in whom we demonstrated a correlation between the severity of injury, sympathetic activation, IL-10 plasma levels and the incidence of infectious complications.

Conclusion

In summary, we suppose that activation of inhibitory neuroimmune pathways like the sympathetic nervous system, but also the hypothalamic-pituitary-adrenal axis, may trigger a systemic anti-inflammatory response syndrome that leads to systemic immunodepression. In this process the catecholamine-mediated systemic IL-10 release that causes monocytic deactivation may be a key mechanism.

Keywords

brain injury critical illness immunodepression infection inflammation prognosis

Introduction

Brain injury has been found to be an independent risk factor for infectious complications in polytrauma patients [1]. It has been reported that early pneumonia occurs in 40% of patients with closed head injury [2,3]. Moreover, brain injury is associated with the appearance of different cytokines [e.g. interleukin (IL)-1β, IL-6, IL-8, IL-10] in the cerebrospinal fluid [4,5,6,7]. Interestingly, high levels of proinflammatory cytokines in the brain and an elevated intracranial pressure (ICP) lead to an activation of neuroimmune pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, which correlates with the severity of injury and an unfavourable prognosis [8,9,10]. Because monocytes and macrophages are the main targets of the immunomodulatory action of both glucocorticoids and catecholamines, alterations of these immunologically important cells should reflect the brain impact on the systemic postinjury immunodepression [11,12,13]. Indeed, monocytic alterations such as impaired endotoxin-induced cytokine production and a diminished major histocompatibility complex (MHC) class II antigen [human leucocyte antigen (HLA)-DR] expression occurred in patients who developed infectious complications after surgery, major trauma and burn injury [14,15,16,17,18]. An important mediator of monocytic deactivation is the anti-inflammatory cytokine IL-10. This cytokine inhibits the production of proinflammatory cytokines [eg tumour necrosis factor (TNF)-α] and is a major depressor of antigen presentation and specific cellular immunity through the reduction of MHC class II antigen expression and IL-12 production [19,20]. Interestingly, enhanced systemic IL-10 levels have been suggested to contribute to postinjury immunodepression by us and others [21,22,23].

We performed several studies to establish a link between brain-injury triggered sympathetic activation, systemic IL-10 release and immunodepression. In vitro, we investigated the impact of catecholamines on monocyte function. Furthermore, we developed two animal models in order to study the importance of proinflammatory brain cytokines and an increased ICP for sympathetic activation, systemic IL-10 release and altered immunoreactivity. Finally, we checked the significance of the in vitro and animal data in neurosurgical and accidentally brain-injured patients.

Catecholamines induce interleukin-10 release from monocytes in vitro

Monocytes/macrophages play a critical role in immunity as regulators of homeostasis, antigen-presenting cells, and effector cells in infection, tumour surveillance and wounding [9,10,14,15,24,25,26,27].

The cytokines secreted by monocytes/macrophages in inflammation fall into three categories. First are those that promote or mediate the acute inflammatory response as well as the type 1 response of lymphocytes. These include TNF-α, IL-1, IL-6, the IL-12 heterodimer (p70) and a range of chemotactic proteins such as IL-8 [28,29,30,31,32]. A second category of cytokines are those that inhibit inflammation. Included are IL-10, transforming growth factor-β and IL-1 receptor antagonist [24,33,34,35,36]. Finally, monocytes/macrophages have been shown to release cytokines that promote tissue repair and homeostasis after or during inflammation, such as platelet-derived and fibroblast growth factors [29]. Consequently, monocytes/macrophages regulate the inflammatory and immune response through both suppressive and enhancing signals.

Furthermore, monocytes/macrophages themselves can be activated and deactivated [24]. Recently, we showed that monocytic deactivation is associated with a much higher risk of infection and with a high mortality in established sepsis [25,37,38]. Deactivated monocytes are characterized by markedly reduced HLA-DR expression, diminished antigen-presenting and respiratory burst capacities, and a profoundly decreased ability to produce proinflammatory cytokines like TNF-α after ex vivo endotoxin stimulation [25,38,39]. An important mediator of monocytic deactivation is IL-10 [19,28,40,41].

In addition to direct immunoregulatory loops (eg IL-10 induction in monocytes by TNF-α [42]), monocytic deactivation or switch of these immune cells into an anti-inflammatory action can be triggered by neuroimmune pathways. Thus, monocytes/macrophages express glucocorticoid and β-adrenergic receptors [24,43]. Catecholamines act on their target cells through binding to cell-surface adrenergic receptors. These adrenoreceptors are divided into two classes – α and β – from which the latter are more widely expressed on immune cells [43]. β-adrenoreceptors are coupled intracellularly to the guanosine triphosphate-binding protein of the adenylate cyclase complex, resulting in a rise in intracellular cyclic adenosine monophosphate (AMP) levels and protein kinase A activation upon stimulation. In this way, catecholamines or other cyclic AMP-elevating drugs can regulate cytokine production in monocytes [12,42,44,45] (Fig. 1).

In order to establish a link between sympathetic activation and monocytic deactivation and anti-inflammatory function, we tested whether catecholamines can trigger IL-10 release from peripheral blood mononuclear cells and purified monocytes in vitro [8]. Indeed, both catecholamines (adrenaline and noradrenaline) and their second messenger (dibutyryl-cyclic AMP) induced a marked IL-10 release in otherwise unstimulated peripheral blood mononuclear cells from healthy donors within 15 min. Separation experiments revealed that monocytes were responsible for this effect. The adrenaline- and noradrenaline-triggered IL-10 induction was dose-dependently inhibited by preincubation with the β2-adrenoreceptor antagonist propranolol. The protein kinase A inhibitor H89 blocked IL-10 secretion in response to both catecholamines and dibutyryl-cyclic AMP [8].

Our in vitro data confirmed other studies [43] that demonstrated that catecholamines and adrenergic agonists can modulate various aspects of the immune response (initial, proliferative and effector phases), altering such functions as cytokine production, lymphocyte proliferation and antibody secretion. Thus, it has been shown that catecholamines inhibit the monocytic production of TNF-α after endotoxin stimulation [11,45]. Furthermore, van der Poll et al [12] demonstrated that pre-exposure of mononuclear cells to adrenaline or noradrenaline not only inhibits endotoxin-induced TNF-α production but also increases the endotoxin-induced IL-10 release. These findings were also proved in vivo using catecholamine infusions in healthy volunteers [12].

In summary, catecholamines may cause a switch of monocytes/macrophages into an anti-inflammatory action and may act to dampen excessive proinflammatory effects of the cytokine network during early phases of systemic insults.
Figure 1

Mechanism of the brain injury-induced interleukin (IL)-10 release that leads to systemic immunodepression. Proinflammatory cytokines are produced in the brain after infection, injury and ischaemia. Microglia, astrocytes and blood-derived immune cells are the main sources for this cytokine production. These brain cytokines (especially IL-1β) and/or an increased intracranial pressure (ICP) may activate inhibitory neuroimmune pathways, such as the sympathetic nervous system. This leads to high catecholamine levels in plasma. Immune cells, especially monocytes, carry β-adrenoreceptors on their surface that mediate the catecholamine-induced increase of intracellular levels of cyclic adenosine monophosphate (cAMP) as second messenger for the regulation of monocytic cytokine production. Thus, catecholamines and cyclic AMP-elevating drugs can inhibit the production of IL-1β, IL-12 heterodimer and tumour necrosis factor (TNF)-α and increase the synthesis of the potent anti-inflammatory and immunosuppressive cytokine IL-10, resulting in the downregulation of monocytic proinflammatory and accessory functions. By this mechanism, catecholamines may switch the monocytes/macrophages to a predominant anti-inflammatory action. HLA, human leukocyte antigen.

Brain IL-1beta and increased ICP induce systemic IL-10 release through stimulation of the sympathetic nervous system in vivo

Interestingly, in recent investigations an anatomical link between the autonomic nervous system and the immune system was established. Primary and secondary lymphoid organs are thus innervated extensively by noradrenergic sympathetic nerve fibres [43,46]. Additionally, mediators of the immune system (especially IL-1β) can enhance splenic sympathetic nerve activity and increase noradrenaline turnover in the spleen, lung, diaphragm and pancreas [47,48,49]. Taken together, the in vivo situation seems to be characterized by a close mutual regulation of the immune and the sympathetic nervous systems.

Considering brain injury, cytokines produced in the brain after trauma as well as an increased ICP can enhance sympathetic nerve activity. Therefore, we investigated the role of brain cytokines and increased ICP in the systemic IL-10 release via the catecholamine-β2-adrenoreceptor pathway using different animal models.

First, we tested the consequences of an acutely increased ICP for the IL-10 plasma levels [8]. In rats, an elevation of ICP to 60 mmHg was achieved by inflation of a subdurally placed Forgarty catheter. Furthermore, one animal group was additionally treated with the β2-adrenoreceptor antagonist propranolol by intravenous infusion during the whole observation period. Using this approach we showed that 30 min after ongoing elevated ICP, IL-10 plasma levels were significantly raised. Moreover, the systemic IL-10 increase was completely prevented by parallel infusion of the β2-adrenoreceptor antagonist propranolol, demonstrating the pivotal role of catecholamines for this effect [8].

In order to study the importance of brain cytokines for the systemic immune alterations, an animal model of chronic intracerebral infusion of different proinflammatory cytokines was established [23]. Using this model, we were able to demonstrate that continuous intracerebroventricular infusion of IL-1β (but not TNF-α) at 10 ng/h significantly diminished the endotoxin-induced TNF-α secretion capacity in whole-blood cell cultures, whereas the IL-10 production was increased 4 h after initiation of the infusion [50]. Remarkably, the brain IL-1β-induced early IL-10 peak was prevented by the β2-adrenoreceptor antagonist propranolol [50]. Furthermore, intracerebroventricular bolus injections of IL-1β (100ng) also caused a rapid systemic IL-10 after 30 min, which was comparable to the IL-10 release after ICP increase (unpublished data). Finally, intravenous infusion of catecholamines produced the same effect, with increase in IL-10 plasma levels within minutes (unpublished data).

Interestingly, we showed that brain cytokines and sympathetic activation may also participate in the changes in blood immune cell numbers after brain injury [51]; intra-cerebroventricular infusion of IL-1β but not TNF-α dramatically increased neutrophil counts, whereas lymphocyte numbers dropped. Remarkably, administration of the β -adrenoreceptor antagonist propranolol prevented the decrease in lymphocytes and diminished the neutrophilia after intracerebroventricular infusion of IL-1β.

In conclusion, our in vivo data in rats completely confirmed the in vitro results of a catecholamine-triggered rapid IL-10 release. Moreover, they gave strong evidence for the involvement of this mechanism in brain-mediated immunodepression. Thus, in both models of brain injury (ICP increase and intracerebral IL-1β infusion) a rapid systemic IL-10 release was found, which was mediated through the activation of the sympathetic nervous system.

Sympathetic activation is involved in systemic immunodepression after neurosurgery and accidental brain injury

In several clinical studies we demonstrated that neurosurgical procedures are associated with a postoperative cytokine release into the cerebrospinal fluid and a decreased monocytic HLA-DR expression - a sign of systemic immunodepression. If the percentage of monocytes that express HLA-DR molecules was lower than 30% during the first 3 days after neurosurgery, this was closely related to the development of infectious complications (predictive value 0.9) [8,9,10,52]. This monocytic deactivation was linked to a brain cytokine-induced stimulation of the HPA axis [10,53].

Our studies also revealed that stimulation of the HPA axis is not the only mechanism involved in monocytic deactivation after brain surgery/injury, however. We found a strong effect of tumour location on the postoperative immunological changes after elective neurosurgery [8]. Almost exclusively, patients with infratentorial tumours with brain-stem compression showed a marked systemic release of the anti-inflammatory cytokine IL-10 4–8 h after neurosurgery. These patients, however, also had strong intraoperative signs of sympathetic activation, such as increases in systolic blood pressure. Therefore, we assumed that sympathetic activation, probably induced by brain IL-1β or brain-stem irritation/compression (manipulation, increased ICP), could be of major importance for the IL-10 release and immunodepression in neurosurgical patients.

To further study the effect of brain-stem compression on the IL-10 plasma levels and the monocytic HLA-DR expression we analyzed patients with an ICP greater than 20 mmHg after selective head injury, or intracerebral haemorrhage or infarction [8]. We showed that an elevated ICP in patients with brain insults was regularly associated with massive sympathetic activation, increased IL-10 plasma levels and a severely decreased HLA-DR expression on monocytes – signs of systemic immunodepression.

Finally, it should be emphasized again that IL-10 not only downregulates monocytic MHC class II expression and antigen-presenting capacity. It also inhibits monocytic production of proinflammatory and the specific cellular immune response-stimulating cytokines, including IL-1β, IL-12 heterodimer and TNF-α, while inducing secretion of IL-1 receptor antagonist that competitively inhibits IL-1 activity (Fig. 1) [22,33,35,36,54]. Thus, the rapid catecholamine-mediated systemic release of the immunoinhibitory cytokine IL-10 might be a key mechanism in brain injury-induced systemic immunodepression.

It also has to be considered, however, that increased intra-cellular cyclic AMP levels, as induced by catecholamines, have been demonstrated to have marked IL-10-independent immunosuppressive effects in monocytes (Fig. 1) [42]. Lastly, other immune-inhibitory cytokines such as transforming growth factor-β can be triggered by catecholamines and may further enhance their immunosuppressive action [55].

Conclusion

In summary, our data regarding brain injury suggest that brain-derived cytokines as well as direct brain-stem irritation can trigger strong sympathetic activation leading to a systemic IL-10 release and monocytic deactivation which, as a sign of severe systemic immunodepression, is associated with a high risk of infectious complications. The likely pathophysiological role of this neuroimmunological pathway of immune suppression is further underlined by the fact that, apart from brain injury, 'sympathetic storm' with elevated plasma catecholamine concentrations can also result from other stressful events, such as myocardial infarction, sepsis and stressful episodes [56,57,58,59,60,61].

Authors’ Affiliations

(1)
Department of Neurosurgery, Charité-Campus Virchow-Klinikum, Humboldt University of Berlin
(2)
Institute of Medical Immunology, Charité-Campus Charité-Mitte, Humboldt University of Berlin

References

  1. Rodriguez JL, Gibbons KJ, Bitzer LG, et al.: Pneumonia: incidence, risk factors, and outcome in injured patients. J Trauma 1991, 31: 907-912.View ArticlePubMedGoogle Scholar
  2. Hsieh AH, Bishop MJ, Kubilis PS, et al.: Pneumonia following closed head injury. Am Rev Respir Dis 1992, 146: 290-294.View ArticlePubMedGoogle Scholar
  3. Piek J, Chesnut RM, Marshall LF, et al.: Extracranial complications of severe head injury. J Neurosurg 1992, 77: 901-907.View ArticlePubMedGoogle Scholar
  4. Beamer NB, Coull BM, Clark WM, et al.: Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Ann Neurol 1995, 37: 800-805.View ArticlePubMedGoogle Scholar
  5. Fassbender K, Rossol S, Kammer T, et al.: Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci 1994, 122: 135-139. 10.1016/0022-510X(94)90289-5View ArticlePubMedGoogle Scholar
  6. Kossmann T, Hans VH, Imhof HG, et al.: Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 1995, 4: 311-317.View ArticlePubMedGoogle Scholar
  7. Ott L, McClain CJ, Gillespie M, et al.: Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 1994, 11: 447-472.View ArticlePubMedGoogle Scholar
  8. Woiciechowsky C, Asadullah K, Nestler D, et al.: Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nature Med 1998, 4: 808-813.View ArticlePubMedGoogle Scholar
  9. Asadullah K, Woiciechowsky C, Döcke WD, et al.: Immunodepression following neurosurgical procedures. Crit Care Med 1995, 23: 1976-1983. 10.1097/00003246-199512000-00006View ArticlePubMedGoogle Scholar
  10. Asadullah K, Woiciechowsky C, Döcke WD, 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 Emerg Med 1996, 2: 184-190.View ArticleGoogle Scholar
  11. van-der PT, Jansen J, Endert E, et al.: Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood. Infect Immun 1994, 62: 2046-2050.Google Scholar
  12. van der Poll T, Coyle SM, Barbosa K, et al.: Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 1996, 97: 713-719.PubMed CentralView ArticlePubMedGoogle Scholar
  13. Kapcala LP, Chautard T, Eskay RL: The protective role of the hypothalamic-pituitary-adrenal axis against lethality produced by immune, infectious, and inflammatory stress. Ann N Y Acad Sci 1995, 771: 419-437.View ArticlePubMedGoogle Scholar
  14. Lennard TW, Shenton BK, Borzotta A, et al.: The influence of surgical operations on components of the human immune system. Br J Surg 1985, 72: 771-776.View ArticlePubMedGoogle Scholar
  15. Guillou PJ: Biological variation in the development of sepsis after surgery or trauma. Lancet 1993, 342: 217-220. 10.1016/0140-6736(93)92303-BView ArticlePubMedGoogle Scholar
  16. Miller Graziano CL, Szabo G, Kodys K, et al.: Aberrations in post-trauma monocyte (MO) subpopulation: role in septic shock syndrome. J Trauma 1990, 30: S86-S96.View ArticlePubMedGoogle Scholar
  17. Gibbons RA, Martinez OM, Lim RC, et al.: 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 1989, 75: 371-375.PubMed CentralPubMedGoogle Scholar
  18. Cheadle WG, Hershman MJ, Wellhausen SR, et al.: HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 1991, 161: 639-645.View ArticlePubMedGoogle Scholar
  19. Fiorentino DF, Zlotnik A, Mosmann TR, et al.: IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991, 147: 3815-3822.PubMedGoogle Scholar
  20. Mosmann TR: Interleukin-10. In: The Cytokine Handbook. Edited by Thomson A. London: Academic Press 1994, 223-237.Google Scholar
  21. Döcke WD, Jacobi CA, Stösslein R, et al.: Rapid IL-10 release after major surgery may contribute to post-operative immunodepression [abstract]. Immunobiology 1996, 196: 59.Google Scholar
  22. Sherry RM, Cue JI, Goddard JK, et al.: Interleukin-10 is associated with the development of sepsis in trauma patients. J Trauma 1996, 40: 613-616.View ArticlePubMedGoogle Scholar
  23. Schöning B, Elepfandt P, Lanksch WR, et al.: Continuous infusion of proinflammatory cytokines into the brain to study brain cytokine induced local and systemic immune effects. Brain Res Brain Res Protoc 1999, 1: 217-222. 10.1016/S1385-299X(99)00022-7View ArticleGoogle Scholar
  24. Celada A, Nathan C: Macrophage activation revisited. Immunol Today 1994, 15: 100-102. 10.1016/0167-5699(94)90150-3View ArticlePubMedGoogle Scholar
  25. Döcke WD, Randow F, Syrbe U, et al.: Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nature Med 1997, 3: 678-681.View ArticlePubMedGoogle Scholar
  26. Hoch RC, Rodriguez R, Manning T, et al.: Effects of accidental trauma on cytokine and endotoxin production [see comments]. Crit Care Med 1993, 21: 839-845.View ArticlePubMedGoogle Scholar
  27. Livingston DH, Appel SH, Wellhausen SR, et al.: Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch Surg 1988, 123: 1309-1312.View ArticlePubMedGoogle Scholar
  28. Ottaviani E, Franceschi C: The invertebrate phagocytic immunocyte: clues to a common evolution of immune and neuroendocrine systems. Immunol Today 1997, 18: 169-174. 10.1016/S0167-5699(97)84663-4View ArticlePubMedGoogle Scholar
  29. Deuel TF, Kawahara RS, Mustoe TA, et al.: Growth factors and wound healing: platelet-derived growth factor as a model cytokine. Annu Rev Med 1991, 42: 567-584. 10.1146/annurev.me.42.020191.003031View ArticlePubMedGoogle Scholar
  30. Unanue ER: Makrophages, antigen-presentig cells and the phenomena of antigen handling and presentation. In : Fundamental Immunology. Edited by Paul WE. New York: Raven Press 1993, 111-138.Google Scholar
  31. Trinchieri G: Proinflammatory and immunoregulatory functions of interleukin-12. Int Rev Immunol 1998, 16: 365-396.View ArticlePubMedGoogle Scholar
  32. Trinchieri G: Immunobiology of interleukin-12. Immunol Res 1998, 17: 269-278.View ArticlePubMedGoogle Scholar
  33. Howard M, O'Garra A: Biological properties of interleukin 10. Immunol Today 1992, 13: 198-200. 10.1016/0167-5699(92)90153-XView ArticlePubMedGoogle Scholar
  34. Mathiesen T, Edner G, Ulfarsson E, et al.: Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage. J Neurosurg 1997, 87: 215-220.View ArticlePubMedGoogle Scholar
  35. Bogdan C, Paik J, Vodovotz Y, et al.: Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem 1992, 267: 23301-23308.PubMedGoogle Scholar
  36. Pretolani M, Goldman M: IL-10: a potential therapy for allergic inflammation? Immunol Today 1997, 18: 277-280. 10.1016/S0167-5699(97)80023-0View ArticlePubMedGoogle Scholar
  37. Volk HD, Reinke P, Krausch D, et al.: Monocyte deactivation: rationale for a new therapeutic strategy in sepsis. Intens Care Med 1996, 22: 474-481.View ArticleGoogle Scholar
  38. Döcke WD, Platzer C, Syrbe U, et al.: Monocytic deactivation in fatal septic disease: role of tumor necrosis factor-alpha and interleukin-10. In MOF, MODS and SIRS. Basic Mechanisms in Inflammation and Tissue Injury. Edited by Faist E, Baue A, Schildberg F. Lengerich: Pabst Science Publishers 1996, 162-168.Google Scholar
  39. Volk HD, Thieme M, Ruppe U, et al.: Alterations in function and phenotype of monocytes from patients with septic disease: predictive value and new therapeutic strategies. In: Host Defense Dysfunction in Trauma, Shock and Sepsis. Edited by Faist E, Meakins JL, Schildberg F. Berlin, Heidelberg: Springer, 1993, 365-371.View ArticleGoogle Scholar
  40. de-Waal MR, Abrams J, Bennett B, et al.: Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991, 174: 1209-1220.View ArticleGoogle Scholar
  41. Cavaillon JM: Cytokines and macrophages. Biomed Pharmacother 1994, 48: 445-453. 10.1016/0753-3322(94)90005-1View ArticlePubMedGoogle Scholar
  42. Platzer C, Meisel C, Vogt K, et al.: Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol 1995, 7: 517-523.View ArticlePubMedGoogle Scholar
  43. Madden KS, Sanders VM, Felten DL: Catecholamine influences and sympathetic neural modulation of immune responsiveness. Annu Rev Pharmacol Toxicol 1995, 35: 417-448. 10.1146/annurev.pa.35.040195.002221View ArticlePubMedGoogle Scholar
  44. Meisel C, Vogt K, Platzer C, et al.: Differential regulation of monocytic tumor necrosis factor-alpha and interleukin-10 expression. Eur J Immunol 1996, 26: 1580-1586.View ArticlePubMedGoogle Scholar
  45. Severn A, Rapson NT, Hunter CA, et al.: Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol 1992, 148: 3441-3445.PubMedGoogle Scholar
  46. Croiset G, Heijnen CJ, vander Wal WE, et al.: A role for the autonomic nervous system in modulating the immune response during mild emotional stimuli. Life Sci 1990, 46: 419-425. 10.1016/0024-3205(90)90085-6View ArticlePubMedGoogle Scholar
  47. Terao A, Oikawa M, Saito M: Tissue-specific increase in norepinephrine turnover by central interleukin-1, but not by interleukin-6, in rats. Am J Physiol 1994, 266: R400-R404.PubMedGoogle Scholar
  48. Ichijo T, Katafuchi T, Hori T: Central interleukin-1 beta enhances splenic sympathetic nerve activity in rats. Brain Res Bull 1994, 34: 547-553. 10.1016/0361-9230(94)90139-2View ArticlePubMedGoogle Scholar
  49. Shimizu N, Hori T, Nakane H: An interleukin-1 beta-induced noradrenaline release in the spleen is mediated by brain corticotropin-releasing factor: an in vivo microdialysis study in conscious rats. Brain Behav Immun 1994, 8: 14-23. 10.1006/brbi.1994.1002View ArticlePubMedGoogle Scholar
  50. Woiciechowsky C, Schöning B, Daberkow N, et al.: Brain-IL-1β induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Brain Res 1999, 816: 563-571. 10.1016/S0006-8993(98)01238-4View ArticlePubMedGoogle Scholar
  51. Woiciechowsky C, Schöning B, Daberkow N, et al.: Brain IL-1β increases neutrophil and decreases lymphocyte counts through stimulation of neuroimmune pathways. Neurobiology Dis 1999, 6: 200-208. 10.1006/nbdi.1999.0242View ArticleGoogle Scholar
  52. Woiciechowsky C, Asadullah K, Nestler D, et al.: Different release of cytokines into the cerebrospinal fluid following surgery for intra- and extra-axial brain tumours. Acta Neurochir Wien 1997, 139: 619-624.View ArticlePubMedGoogle Scholar
  53. Woiciechowsky C, Asadullah K, Döcke WD, et al.: Immunodepression following neurosurgical procedures resulting from activation of the neuroendocrine system [abstract]. Zentralbl Neurochir 1997, 58: 86.Google Scholar
  54. Fiorentino DF, Zlotnik A, Vieira P, et al.: IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 1991, 146: 3444-3451.PubMedGoogle Scholar
  55. Fisher SA, Absher M: Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro . Am J Physiol 1995, 268: C910-C917.PubMedGoogle Scholar
  56. Sigurdsson A, Held P, Swedberg K: Short- and long-term neurohormonal activation following acute myocardial infarction. Am Heart J 1993, 126: 1068-1076.View ArticlePubMedGoogle Scholar
  57. Bohm H, Laimer H, Douglas T: Plasma ANP, noradrenaline, lactate concentrations during standardized ergometric stress in post-infarct patients. Evaluation of myocardial stress function with reference to limits of exercise therapy [in German]. Z Kardiol 1991, 80 (suppl 8): 85.Google Scholar
  58. Blandini F, Martignoni E, Sances E, et al.: Combined response of plasma and platelet catecholamines to different types of short-term stress. Life Sci 1995, 56: 1113-1120. 10.1016/0024-3205(95)00048-BView ArticlePubMedGoogle Scholar
  59. Kvetnansky R, Pacak K, Fukuhara K, et al.: Sympathoadrenal system in stress. Interaction with the hypothalamic–pituitary–adrenocortical system. Ann N Y Acad Sci 1995, 771: 131-158.View ArticlePubMedGoogle Scholar
  60. Roozen AW, Tsuma VT, Magnusson U: Effects of short-term restraint stress on plasma concentrations of catecholamines, beta-endorphin, and cortisol in gilts. Am J Vet Res 1995, 56: 1225-1227.PubMedGoogle Scholar
  61. Parrott RF, Misson BH, de la Riva CF: Differential stressor effects on the concentrations of cortisol, prolactin and catecholamines in the blood of sheep. Res Vet Sci 1994, 56: 234-239.View ArticlePubMedGoogle Scholar

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