Skip to main content

Advertisement

SpringerLink
Log in

Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH).

Design and setting

Clinical study in a neurosurgical intensive care unit.

Patients and participants

Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover.

Intervention

Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th–10th day after the SAH.

Measurements and results

SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7–10 days after the insult, 3–4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7–10 days after the SAH, but the plasma level of IL-6 decreased significantly 7–10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers.

Conclusions

Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Moynihan J, Kruszewska B, Madden K, Callahan T (2004) Sympathetic nervous system regulation of immunity. J Neuroimmunol 147:87–90

    Article  PubMed  CAS  Google Scholar 

  2. Elenkov I, Wilder R, Chrousos G, Vizi S (2000) The sympathetic nerve – an integrative interface between two super systems: the brain and the immune system. Pharmacol Rev 52:595–638

    PubMed  CAS  Google Scholar 

  3. Maier S, Watkins L (1998) Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behaviour, mood and cognition. Psychol Rev 105:83–107

    Article  PubMed  CAS  Google Scholar 

  4. Watkins L, Maier S (2005) Immune regulation of central nervous system functions. From sickness responses to pathological pain. J Intern Med 257:139–155

    Article  PubMed  CAS  Google Scholar 

  5. Felten D, Felten S, Bellinger D, Carlsson S, Ackerman K, Madden K, Olschowki J, Livnat S (1987) Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev 100:225–260

    Article  PubMed  CAS  Google Scholar 

  6. Felten D, Felten S, Bellinger D, Madden K (1993) Fundamental aspects of neural-immune signaling. Psychother Psychosom 60:46–56

    Article  PubMed  CAS  Google Scholar 

  7. Black P (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 16:622–653

    Article  PubMed  CAS  Google Scholar 

  8. Connor T, Brewer C, Kelley J, Harkin A (2005) Acute stress response suppresses pro-inflammatory cytokines TNF-alfa and IL-1beta independent of a catecholamine-driven increase in IL-10 production. J Neuroimmunol 159:119–128

    Article  PubMed  CAS  Google Scholar 

  9. Volk T, Döpfmer U, Schmutzler M, Rimpau S, Schnitzler H, Konertz W, Hoeflich C, Döcke W, Spies C, Volk H, Kox W (2003) Stress induced IL-10 does not seem to be essential for early monocyte deactivation following cardiac surgery. Cytokine 24:237–243

    Article  PubMed  CAS  Google Scholar 

  10. van der Poll T, Jansen J, Endert E, Sauerwein H, van Deventer S (1994) Noradrenaline inhibits lipopolysaccharide-induced tumour necrosis factor and interleukin 6 production in human whole blood. Infect Immun 62:2046–2050

    PubMed  Google Scholar 

  11. Bürger A, Benicke M, Deten A, Zimmer HG (2001) Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts. AJP Heart 281:14–21

    Google Scholar 

  12. Meisel C, Schwab JM, Prass K, Meisel A, Dirnag U (2005) Central nervous system injury induced immune deficiency syndrome. Nat Rev/Neuroscience 6:775–786

    Article  CAS  Google Scholar 

  13. Dhabhar F (2003) Stress, leukocyte trafficking, and the augmentation of skin immune function. Ann N Y Acad Sci 992:205–217

    PubMed  CAS  Google Scholar 

  14. Dhabhar F, McEven B (1997) Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leucocyte trafficking. Brain Behav Immun 11:286–306

    Article  CAS  Google Scholar 

  15. Tracey K (2002) The inflammatory reflex. Nature 420:853–859

    Article  PubMed  CAS  Google Scholar 

  16. Macmillan C, Grant I, Andrews P (2002) Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intensive Care Med 28:1012–1023

    Article  PubMed  CAS  Google Scholar 

  17. Cruickshank JM, Neil-Dwyer G, Stott AW (1974) Possible role of catecholamines, corticosteroids and potassium in production of electrocardiographic abnormalities associated with subarachnoid haemorrhage. Br Heart J 36:697–706

    PubMed  CAS  Google Scholar 

  18. Dilraj A, Botha JB, Rambiritch V, Miller R, van Dellen JR (1992) Levels of catecholamines in plasma and cerebrospinal fluid in aneurysmal subarachnoid hemorrhage. Neurosurg 31:42–51

    CAS  Google Scholar 

  19. Naredi S, Lambert G, Edén E, Zäll S, Runnerstam M, Rydenhag B, Friberg P (2000) Increased sympathetic nervous activity in patients with non-traumatic subarachnoid hemorrhage. Stroke 31:901–906

    PubMed  CAS  Google Scholar 

  20. Dampney R, Moon E (1980) Role of ventrolateral medulla in vasomotor response to cerebral ischemia. Am J Physiol 239:349–358

    Google Scholar 

  21. Reis D, Morrison S, Ruggiero D (1988) The C1 area of the brainstem in tonic and reflex control of blood pressure. Hypertension 11:18–23

    Google Scholar 

  22. Sun M, Reis D (1994) Hypoxia selectively excites vasomotor neurons of rostral ventrolateral medulla in rats. Am J Physiol 266:R245–R256

    PubMed  CAS  Google Scholar 

  23. Yoshimoto Y, Tanaka Y, Hoya K (2001) Acute systemic inflammatory response syndrome in subarachnoid hemorrhage. Stroke 32:1989–1993

    PubMed  CAS  Google Scholar 

  24. Hidetoshi K, Takashi S (1989) Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71:741–746

    Google Scholar 

  25. Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, Fritzinger M, Horn P, Vajkoczy P, Kreisel S, Brunner J, Schmiedek P, Hennerici M (2001) Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries Neurol Neurosurg Psychiatry 70:534–537

    CAS  Google Scholar 

  26. Mathiesen T, Andersen B, Loftenius A, von Holst H (1993) Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 78:562–567

    PubMed  CAS  Google Scholar 

  27. Kasuya H, Shimizu T (1989) Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71:741–746

    Article  PubMed  CAS  Google Scholar 

  28. Fisher CM, Kistler JP, Davis JM (1980) Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1–9

    PubMed  CAS  Google Scholar 

  29. Hunt WE, Hess RM (1968) Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28:14–20

    Article  PubMed  CAS  Google Scholar 

  30. Eisenhofer G (2005) Sympathetic nerve function. Assessment by radioisotope dilution analysis. Clin Auton Res 15:264–283

    Article  PubMed  Google Scholar 

  31. Esler M, Jackmann G, Bobik A, Kelleher D, Jennings G, Leonard P, Skews H, Korner P (1979) Determination of norepinephrine apparent release and clearance in humans. Life Sci 25:1461–1470

    Article  PubMed  CAS  Google Scholar 

  32. Esler M, Jennings G, Leonard P Sacharias N, Burke F, Johns J, Blombery P (1984) Contribution of individual organs to total noradrenaline release in humans. Acta Physiol Scand 527:11–16

    CAS  Google Scholar 

  33. Padgett D, Glaser R (2003) How stress influences the immune response. Trends Immunol 24:444–448

    Article  PubMed  CAS  Google Scholar 

  34. Raßler B, Reißig C, Briest W, Tannapfel A, Zimmer HG (2003) Pulmonary edema and pleural effusion in norepinephrine-stimulated rats – hemodynamic or inflammatory effect? Mol Cell Biochem 250:55–63

    Article  PubMed  Google Scholar 

  35. Fassbender K, Rossol S, Kammer T, Daffertshofer M, Wirth S, Dollman M, Hennerici M (1994) 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 122:135–139

    Article  PubMed  CAS  Google Scholar 

  36. Van Beek J, Elward K, Gasque P (2003) Activation of complement in the central nervous system. Ann N Y Acad Sci 992:56–71

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was performed at Sahlgrenska University Hospital, Göteborg, Sweden. The study was supported by grants from the Regional Health Care Authority of West Sweden, The Göteborg Medical Society, the Swedish Society of Medicine, the Swedish Medical Research Council and the National Health and Medical Council of Australia.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology and Intensive Care, Umeå University Hospital, 901 85, Umeå, Sweden

    Silvana Naredi

  2. Department of Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden

    Gavin Lambert & Peter Friberg

  3. Baker Heart Research Institute, Melbourne, Australia

    Gavin Lambert

  4. Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden

    Stefan Zäll, Elisabeth Edén, Maria Tylman & Anders Bengtsson

  5. Department of Neurosurgery, Sahlgrenska University Hospital, Göteborg, Sweden

    Bertil Rydenhag

Authors
  1. Silvana Naredi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gavin Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Friberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan Zäll
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisabeth Edén
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bertil Rydenhag
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Tylman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anders Bengtsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Silvana Naredi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naredi, S., Lambert, G., Friberg, P. et al. Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage. Intensive Care Med 32, 1955–1961 (2006). https://doi.org/10.1007/s00134-006-0408-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-006-0408-y

Keywords

Search

Navigation