Advertisement

Inflammation Research

, Volume 61, Issue 8, pp 845–852 | Cite as

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study

  • Milo StanisicEmail author
  • Ansgar Oddne Aasen
  • Are Hugo Pripp
  • Karl-Fredrik Lindegaard
  • Jon Ramm-Pettersen
  • Staale Petter Lyngstadaas
  • Jugoslav Ivanovic
  • Ane Konglund
  • Eivind Ilstad
  • Tiril Sandell
  • Omar Ellingsen
  • Terje Sæhle
Original Research Paper

Abstract

Objective and design

Innate immune pro- and anti-inflammatory responses in patients with chronic subdural hematoma (CSDH) were investigated by measuring and comparing the systemic and subdural fluid levels of cytokines.

Materials and method

Cytokine values were analyzed in samples obtained during surgery of 56 adult patients who were operated on for unilateral CSDHs using a Multiplex antibody bead kit.

Results

There were significantly higher levels of the pro-inflammatory IL-2R (p = 0.004), IL-5 (p < 0.001), IL-6 (p < 0.001), and IL-7 (p < 0.001), and anti-inflammatory mediators IL-10 (p < 0.001) and IL-13 (p = 0.002) in CSDH fluid compared with systemic levels. The pro-inflammatory TNF-alpha (p < 0.001), IL-1beta (p < 0.001), IL-2 (p = 0.007) and IL-4 (p < 0.001) were significantly lower in hematoma fluid compared with systemic levels. The ratios between pro- versus anti-inflammatory cytokines were statistically significant higher in CSDH (7.8) compared with systemic levels (1.3).

Conclusions

The innate immune responses occur both locally at the site of CSDH, as well as systematically in patients with CSDH. The local hyper-inflammatory and low anti-inflammatory responses exist simultaneously. The findings suggest poorly coordinated innate immune responses at the site of CSDH that may lead to propagating of local inflammatory process and basically contribute to formation and progression of CSDH.

Keywords

Chronic subdural hematoma Interleukin-2R Interleukin-5 Interleukin-6 Interleukin-7 Interleukin-10 Interleukin-13 

Notes

Acknowledgments

This study was supported by a grant from the Department of Neurosurgery, Oslo University Hospital, Oslo, Norway. We highly acknowledge Mrs Aina Mari Lian for excellent technical assistance and Mrs Annet Tøen for skilled database management.

References

  1. 1.
    Chen JC, Levy ML. Causes, epidemiology, and risk factors of chronic subdural hematoma. Neurosurg Clin North Am. 2000;11:399–406.Google Scholar
  2. 2.
    Weigel R, Schmiedek P, Krauss JK. Outcome of contemporary surgery for chronic subdural haematoma: evidence based review. J Neurol Neurosurg Psychiatry. 2003;74:937–43.PubMedCrossRefGoogle Scholar
  3. 3.
    DE Haines, Harkey HL, al-Mefty O. The “subdural” space: a new look at an outdated concept. Neurosurgery. 1993;32:111–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Mack J, Squier W, Eastman JT. Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol. 2009;39:200–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Reina MA, Casasola ODL, Lopez A, De Andres JA, Mora M, Fernandez A. The origin of the spinal subdural space: ultrastructure findings. Anesth Analg. 2002;94:991–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Frati A, Salvati M, Mainiero F, Ippoliti F, Rocchi G, Raco A, Caroli E, Cantore G, Delfini R. Inflammation markers and risk factors for recurrence in 35 patients with a posttraumatic chronic subdural hematoma: a prospective study. J Neurosurg. 2004;100:24–32.PubMedGoogle Scholar
  7. 7.
    Hirashima Y, Endo S, Kato R, Ohmori T, Nagahori T, Nishijima M, Karasawa K, Nojima S, Takaku A. Platelet-activating factor (PAF) and the development of chronic subdural haematoma. Acta Neurochir (Wien). 1994;129:20–5.CrossRefGoogle Scholar
  8. 8.
    Hong HJ, Kim YJ, Yi HJ, Ko Y, Oh SJ, Kim JM. Role of angiogenic growth factors and inflammatory cytokine on recurrence of chronic subdural hematoma. Surg Neurol. 2009;71:161–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Suzuki M, Endo S, Inada K, Kudo A, Kitakami A, Kuroda K, Ogawa A. Inflammatory cytokines locally elevated in chronic subdural haematoma. Acta Neurochir (Wien). 1998;140:51–5.CrossRefGoogle Scholar
  10. 10.
    Wada T, Kuroda K, Yoshida Y. Local elevation of the anti-inflammatory interleukin-10 in the pathogenesis of chronic subdural hematoma. Neurosurg Rev. 2006;29:242–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Hohenstein A, Erber R, Schilling L, Weigel R. Increased mRNA expression of VEGF within the hematoma and imbalance of angiopoietin-1 and -2 mRNA within the neomembranes of chronic subdural hematoma. J Neurotrauma. 2005;22:518–28.PubMedCrossRefGoogle Scholar
  12. 12.
    Katano H, Kamiya K, Mase M, Tanikawa M, Yamada K. Tissue plasminogen activator in chronic subdural hematomas as a predictor of recurrence. J Neurosurg. 2006;104:79–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Nanko N, Tanikawa M, Mase M, Fujita M, Tateyama H, Miyati T, Yamada K. Involvement of hypoxia-inducible factor-1α and vascular endothelial growth factor in the mechanism of development of chronic subdural hematoma. Neurol Med Chir (Tokyo). 2009;49:379–85.CrossRefGoogle Scholar
  14. 14.
    Shono T, Inamura T, Morioka T, Matsumoto K, Suzuki SO, Ikezaki K, Iwaki T, Fukui M. Vascular endothelial growth factor in chronic subdural haematomas. J Clin Neurosci. 2001;8:411–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Suzuki K, Takano S, Nose T, Doi M, Ohasi N. Increased concentration of vascular endothelial growth factor (VEGF) in chronic subdural hematoma. J Trauma. 1999;46:532–3. (Letter).PubMedCrossRefGoogle Scholar
  16. 16.
    Vaquero J, Zurita M, Cincu R. Vascular endothelial growth-permeability factor in granulation tissue of chronic subdural haematomas. Acta Neurochir (Wien). 2002;144:343–7.CrossRefGoogle Scholar
  17. 17.
    Weigel R, Schilling L, Schmiedek P. Specific pattern of growth factor distribution in chronic subdural hematoma (CSH): evidence for an angiogenic disease. Acta Neurochir (Wien). 2001;143:811–9.CrossRefGoogle Scholar
  18. 18.
    Friede RL, Schachenmayer W. The origin of subdural neomembranes II. Fine structure of neomembranes. Am J Pathol. 1978;92:69–84.PubMedGoogle Scholar
  19. 19.
    Moskala M, Gościński I, Kałuża J, Polar J, Krupa M, Adamek D, Pityński K, Miodoński AJ. Morphological aspects of the traumatic chronic subdural hematoma capsule: SEM studies. Microsc Microanal. 2007;13:211–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Yamashima T, Yamamoto S. The origin of inner membranes in chronic subdural hematomas. Acta Neuropathol. 1985;67:219–25.PubMedCrossRefGoogle Scholar
  21. 21.
    Fujisawa H, Ito H, Kashiwagi S, Nomura S, Toyosawa M. Kallikrein-kinin system in chronic subdural haematomas: Its role in vascular permeability and regulation of fibrinolysis and coagulation. J Neurol Neurosurg Psychiatry. 1995;59:388–94.PubMedCrossRefGoogle Scholar
  22. 22.
    Murakami H, Hirose Y, Sagoh M, Shimizu K, Kojima M, Gotoh K, Mine Y, Hayashi T, Kawase T. Why do chronic subdural hematomas continue to grow slowly and not coagulate? Role of thrombomodulin in the mechanism. J Neurosurg. 2002;96:877–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Nomura S, Kashiwagi S, Fujisawa H, Ito H, Nakamura K. Characterization of local hyperfibrinolysis in chronic subdural hematomas by SDS-PAGE and immunoblot. J Neurosurg. 1994;81:910–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Suzuki M, Kudo A, Kitakami A, Doi M, Kubo N, Kuroda K, Ogawa A. Local hypercoagulative activity precedes hyperfibrinolytic activity in the subdural space during development of chronic subdural haematoma from subdural effusion. Acta Neurochir (Wien). 1998;140:261–6.CrossRefGoogle Scholar
  25. 25.
    Weir B, Gordon P. Factors affecting coagulation: fibrinolysis in chronic subdural fluid collection. J Neurosurg. 1983;58:242–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Kawano N, Suzuki K. Presence of smooth-muscle cells in the subdural neomembrane. J Neurosurg. 1981;54:646–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Sarkar C, Lakhtakia R, Gill SS, Sharma MC, Mahapatra AK, Mehta VS. Chronic subdural haematoma and the enigmatic eosinophil. Acta Neurochir (Wien). 2002;144:983–8.CrossRefGoogle Scholar
  28. 28.
    Dinarello CA. Proinflammatory cytokines. Chest. 2000;118:503–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Li H, Lin X. Positive and negative signalling components involved in TNF-alpha-induced NF-kappaB activation. Cytokine. 2008;41:1–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Apte SH, Baz A, Kelso A, Kienzle N. Interferon-gamma and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells. Proc Natl Acad Sci USA. 2008;105:17475–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Arai K, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836.PubMedCrossRefGoogle Scholar
  32. 32.
    Boyman O, Ramsey C, Kim DM, Sprent J, Surh CD. Il-7/Anti-IL-7 mAb complexes restore T cell development and induce homeostatic T cell expansion without lymphopenia. J Immunol. 2008;180:7265–75.PubMedGoogle Scholar
  33. 33.
    Fry TJ, Mackall CL. Interleukin-7: from bench to clinic. Blood. 2002;99:3892–904.PubMedCrossRefGoogle Scholar
  34. 34.
    Nelson BH, Lord JD, Greenberg PD. Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation. Nature. 1994;369:333–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Schluns KS, Lefrançois L. Cytokine control of memory T-cell development and survival. Nat Rev Immunol. 2003;3:269–79.PubMedCrossRefGoogle Scholar
  36. 36.
    Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol. 2006;6:595–601.PubMedCrossRefGoogle Scholar
  37. 37.
    Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J, Capron A, Capron M. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med. 1994;179:703–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol. 1993;54:1–78.PubMedCrossRefGoogle Scholar
  39. 39.
    Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–78.PubMedCrossRefGoogle Scholar
  40. 40.
    Maruo N, Morita I, Shirao M, Murota S-I. IL-6 increases endothelial permeability in vitro. Endocrinology. 1992;131:710–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Strazynski M, Eble JA, Kresse H, Schönherr E. Interleukin (IL)-6 and IL-10 induce decorin mRNA in endothelial cells, but interaction with fibrillar collagen is essential for its translation. J Biol Chem. 2004;279:21266–70.PubMedCrossRefGoogle Scholar
  42. 42.
    Tilg H, Trehu E, Atkins MB. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: Induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83:113–8.PubMedGoogle Scholar
  43. 43.
    Trinchieri G. Interleukin-12 a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. J Immunol. 1995;13:251–76.CrossRefGoogle Scholar
  44. 44.
    Numasaki M, Fukushi JI, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101:2620–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang Y-H, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol. 1998;16:27–55.PubMedCrossRefGoogle Scholar
  47. 47.
    Moore KW, O’Gara A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Annu Rev Immunol. 1993;11:165–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397–440.PubMedCrossRefGoogle Scholar
  49. 49.
    Moore KW, de Waal MR, Coffman RI, O’Gara A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683–765.PubMedCrossRefGoogle Scholar
  50. 50.
    Seymour RM, Henderson B. Pro-inflammatory-anti-inflammatory cytokine dynamics mediated by cytokine-receptor dynamics in monocytes. IMA J Math Appl Med. 2001;18:159–92.CrossRefGoogle Scholar
  51. 51.
    Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Minty A, Chalon P, Derocq JM, Dumont X, Guillemont JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B, Minty C, Casellas P, Loison G, Lupker J, Schire D, Ferrara P, Caput D. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature. 1993;362:248–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Schlag G, Redl H. Mediators of injury and inflammation. World J Surg. 1996;20:406–10.PubMedCrossRefGoogle Scholar
  54. 54.
    Stahel PF, Morganti-Kossmann MC, Kossmann T. The role of the complement system in traumatic brain injury. Brain Res Rev. 1998;27:243–56.PubMedCrossRefGoogle Scholar
  55. 55.
    Keel M, Trentz O. Pathophysiology of polytrauma. Injury. 2005;36:691–709.PubMedCrossRefGoogle Scholar
  56. 56.
    Schmidt OI, Heyde CE, Ertel W, Stahel PF. Closed head injury-an inflammatory disease? Brain Res Rev. 2005;48:388–99.PubMedCrossRefGoogle Scholar
  57. 57.
    Liew FY, McInnes IB. The role of innate mediators in inflammatory response. Mol Immunol. 2002;38:887–90.PubMedCrossRefGoogle Scholar
  58. 58.
    McInnes IB, Gracie JA. Interleukin-15: a new cytokine target for the treatment of inflammatory diseases. Curr Opin Pharmacol. 2004;4:392–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Milo Stanisic
    • 1
    Email author
  • Ansgar Oddne Aasen
    • 2
    • 5
  • Are Hugo Pripp
    • 3
  • Karl-Fredrik Lindegaard
    • 1
    • 5
  • Jon Ramm-Pettersen
    • 1
  • Staale Petter Lyngstadaas
    • 4
  • Jugoslav Ivanovic
    • 1
  • Ane Konglund
    • 1
  • Eivind Ilstad
    • 1
  • Tiril Sandell
    • 1
  • Omar Ellingsen
    • 1
  • Terje Sæhle
    • 1
  1. 1.Department of NeurosurgeryOslo University HospitalOsloNorway
  2. 2.Institute of Surgical Research RikshospitaletOslo University HospitalOsloNorway
  3. 3.Biostatistics and Epidemiology UnitOslo University HospitalOsloNorway
  4. 4.Department of Biomaterials, Faculty of DentistryUniversity of OsloOsloNorway
  5. 5.Faculty of MedicineUniversity of OsloOsloNorway

Personalised recommendations