Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 2004 Aug;13(4):275–283. doi: 10.1080/09629350400003100

Circulating cytokine profile in anti-neutrophilic cytoplasmatic autoantibody-associated vasculitis: prediction of outcome?

Sophie Ohlsson 1, Jörgen Wieslander 1, Mårten Segelmark 1
PMCID: PMC1781567  PMID: 15545059

Abstract

AIMS: The anti-neutrophilic cytoplasmatic autoantibody-associated vasculitides (AASV) are diseases of relapsing-remitting inflammation. Here we explore the cytokine profile in different phases of disease, looking for pathogenic clues of possible prognostic value. RESULTS: Interleukin (IL)-6, IL-8 and IL-10 were significantly elevated in plasma. Patients in the stable phase who subsequently developed adverse events had higher IL-8 values. Patients in the stable phase who relapsed within 3 months had lower IL-10 values and higher IL-6 levels. CONCLUSIONS: Patients with AASV have raised circulating cytokine levels compared with healthy controls, even during remission. Raised IL-8 seems associated with poor prognosis. Lower levels of IL-10 and higher levels of IL-6 herald a greater risk of relapse. Patients with systemic vasculitis in clinical remission have persistent disease activity, kept under control by inhibitory cytokines.

Full Text

The Full Text of this article is available as a PDF (134.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arimura Y., Minoshima S., Kamiya Y., Tanaka U., Nakabayashi K., Kitamoto K., Nagasawa T., Sasaki T., Suzuki K. Serum myeloperoxidase and serum cytokines in anti-myeloperoxidase antibody-associated glomerulonephritis. Clin Nephrol. 1993 Nov;40(5):256–264. [PubMed] [Google Scholar]
  2. Berdowska A., Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther. 2001 Oct;26(5):319–329. doi: 10.1046/j.1365-2710.2001.00358.x. [DOI] [PubMed] [Google Scholar]
  3. Berger S. P., Seelen M. A., Hiemstra P. S., Gerritsma J. S., Heemskerk E., van der Woude F. J., Daha M. R. Proteinase 3, the major autoantigen of Wegener's granulomatosis, enhances IL-8 production by endothelial cells in vitro. J Am Soc Nephrol. 1996 May;7(5):694–701. doi: 10.1681/ASN.V75694. [DOI] [PubMed] [Google Scholar]
  4. Casselman B. L., Kilgore K. S., Miller B. F., Warren J. S. Antibodies to neutrophil cytoplasmic antigens induce monocyte chemoattractant protein-1 secretion from human monocytes. J Lab Clin Med. 1995 Nov;126(5):495–502. [PubMed] [Google Scholar]
  5. Cockwell P., Brooks C. J., Adu D., Savage C. O. Interleukin-8: A pathogenetic role in antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. Kidney Int. 1999 Mar;55(3):852–863. doi: 10.1046/j.1523-1755.1999.055003852.x. [DOI] [PubMed] [Google Scholar]
  6. Dharnidharka Vikas R., Kwon Charles, Stevens Gary. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002 Aug;40(2):221–226. doi: 10.1053/ajkd.2002.34487. [DOI] [PubMed] [Google Scholar]
  7. Diez-Ruiz A., Tilz G. P., Zangerle R., Baier-Bitterlich G., Wachter H., Fuchs D. Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis. Eur J Haematol. 1995 Jan;54(1):1–8. doi: 10.1111/j.1600-0609.1995.tb01618.x. [DOI] [PubMed] [Google Scholar]
  8. Ferrario F., Rastaldi M. P. Necrotizing-crescentic glomerulonephritis in ANCA-associated vasculitis: the role of monocytes. Nephrol Dial Transplant. 1999 Jul;14(7):1627–1631. doi: 10.1093/ndt/14.7.1627. [DOI] [PubMed] [Google Scholar]
  9. Girndt Matthias, Ulrich Christof, Kaul Harald, Sester Urban, Sester Martina, Köhler Hans. Uremia-associated immune defect: the IL-10-CRP axis. Kidney Int Suppl. 2003 May;(84):S76–S79. doi: 10.1046/j.1523-1755.63.s84.14.x. [DOI] [PubMed] [Google Scholar]
  10. Graziani-Bowering G. M., Graham J. M., Filion L. G. A quick, easy and inexpensive method for the isolation of human peripheral blood monocytes. J Immunol Methods. 1997 Sep 24;207(2):157–168. doi: 10.1016/s0022-1759(97)00114-2. [DOI] [PubMed] [Google Scholar]
  11. Hattar Katja, Bickenbach Annette, Csernok Elena, Rosseau Simone, Grandel Ulrich, Seeger Werner, Grimminger Friedrich, Sibelius Ulf. Wegener's granulomatosis: antiproteinase 3 antibodies induce monocyte cytokine and prostanoid release-role of autocrine cell activation. J Leukoc Biol. 2002 Jun;71(6):996–1004. [PubMed] [Google Scholar]
  12. Hellmich Bernhard, Csernok Elena, Gross Wolfgang L. 20 years with ANCA (antineutrophil cytoplasmic autoantibodies): from seromarker to a major pathogenic player in vasculitis. J Leukoc Biol. 2003 Jul;74(1):1–2. doi: 10.1189/jlb.0403134. [DOI] [PubMed] [Google Scholar]
  13. Hynninen M., Valtonen M., Vaara M., Markkanen H., Kuusela P., Saxen H., Takkunen O. Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients. Eur J Clin Microbiol Infect Dis. 1997 Aug;16(8):587–591. doi: 10.1007/BF02447921. [DOI] [PubMed] [Google Scholar]
  14. Jennette J. C., Wilkman A. S., Falk R. J. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol. 1989 Nov;135(5):921–930. [PMC free article] [PubMed] [Google Scholar]
  15. Lowe Peter R., Galley Helen F., Abdel-Fattah Ashraf, Webster Nigel R. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit Care Med. 2003 Jan;31(1):34–38. doi: 10.1097/00003246-200301000-00005. [DOI] [PubMed] [Google Scholar]
  16. Muller Kobold A. C., Kallenberg C. G., Tervaert J. W. Leucocyte membrane expression of proteinase 3 correlates with disease activity in patients with Wegener's granulomatosis. Br J Rheumatol. 1998 Aug;37(8):901–907. doi: 10.1093/rheumatology/37.8.901. [DOI] [PubMed] [Google Scholar]
  17. Muller Kobold A. C., Kallenberg C. G., Tervaert J. W. Monocyte activation in patients with Wegener's granulomatosis. Ann Rheum Dis. 1999 Apr;58(4):237–245. doi: 10.1136/ard.58.4.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muraközy G., Gaede K. I., Ruprecht B., Gutzeit O., Schürmann M., Schnabel A., Schlaak M., Gross W. L., Müller-Quernheim J. Gene polymorphisms of immunoregulatory cytokines and angiotensin-converting enzyme in Wegener's granulomatosis. J Mol Med (Berl) 2001 Nov;79(11):665–670. doi: 10.1007/s001090100263. [DOI] [PubMed] [Google Scholar]
  19. Noronha I. L., Krüger C., Andrassy K., Ritz E., Waldherr R. In situ production of TNF-alpha, IL-1 beta and IL-2R in ANCA-positive glomerulonephritis. Kidney Int. 1993 Mar;43(3):682–692. doi: 10.1038/ki.1993.98. [DOI] [PubMed] [Google Scholar]
  20. Ohlsson S., Wieslander J., Segelmark M. Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin Exp Immunol. 2003 Mar;131(3):528–535. doi: 10.1046/j.1365-2249.2003.02083.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pecoits-Filho Roberto, Heimbürger Olof, Bárány Peter, Suliman Mohamed, Fehrman-Ekholm Ingela, Lindholm Bengt, Stenvinkel Peter. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis. 2003 Jun;41(6):1212–1218. doi: 10.1016/s0272-6386(03)00353-6. [DOI] [PubMed] [Google Scholar]
  22. Pendergraft W. F., Alcorta D. A., Segelmark M., Yang J. J., Tuttle R., Jennette J. C., Falk R. J., Preston G. A. ANCA antigens, proteinase 3 and myeloperoxidase, are not expressed in endothelial cells. Kidney Int. 2000 May;57(5):1981–1990. doi: 10.1046/j.1523-1755.2000.00048.x. [DOI] [PubMed] [Google Scholar]
  23. Popa E. R., Stegeman C. A., Bos N. A., Kallenberg C. G., Tervaert J. W. Differential B- and T-cell activation in Wegener's granulomatosis. J Allergy Clin Immunol. 1999 May;103(5 Pt 1):885–894. doi: 10.1016/s0091-6749(99)70434-3. [DOI] [PubMed] [Google Scholar]
  24. Ralston D. R., Marsh C. B., Lowe M. P., Wewers M. D. Antineutrophil cytoplasmic antibodies induce monocyte IL-8 release. Role of surface proteinase-3, alpha1-antitrypsin, and Fcgamma receptors. J Clin Invest. 1997 Sep 15;100(6):1416–1424. doi: 10.1172/JCI119662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rastaldi M. P., Ferrario F., Tunesi S., Yang L., D'Amico G. Intraglomerular and interstitial leukocyte infiltration, adhesion molecules, and interleukin-1 alpha expression in 15 cases of antineutrophil cytoplasmic autoantibody-associated renal vasculitis. Am J Kidney Dis. 1996 Jan;27(1):48–57. doi: 10.1016/s0272-6386(96)90030-x. [DOI] [PubMed] [Google Scholar]
  26. Remick Daniel G., Bolgos Gerald R., Siddiqui Javed, Shin Jungsoon, Nemzek Jean A. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock. 2002 Jun;17(6):463–467. doi: 10.1097/00024382-200206000-00004. [DOI] [PubMed] [Google Scholar]
  27. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  28. Segelmark M., Westman K., Wieslander J. How and why should we detect ANCA? Clin Exp Rheumatol. 2000 Sep-Oct;18(5):629–635. [PubMed] [Google Scholar]
  29. Tervaert J. W., van der Woude F. J., Fauci A. S., Ambrus J. L., Velosa J., Keane W. F., Meijer S., van der Giessen M., van der Hem G. K., The T. H. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989 Nov;149(11):2461–2465. doi: 10.1001/archinte.149.11.2461. [DOI] [PubMed] [Google Scholar]
  30. Wikman Agneta, Fagergren Anna, Gunnar O Johansson S., Lundahl Joachim, Jacobson Stefan H. Monocyte activation and relationship to anti-proteinase 3 in acute vasculitis. Nephrol Dial Transplant. 2003 Sep;18(9):1792–1799. doi: 10.1093/ndt/gfg216. [DOI] [PubMed] [Google Scholar]
  31. Yudkin J. S., Kumari M., Humphries S. E., Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000 Feb;148(2):209–214. doi: 10.1016/s0021-9150(99)00463-3. [DOI] [PubMed] [Google Scholar]
  32. Zhou Yihua, Giscombe Ricardo, Huang Deren, Lefvert Ann Kari. Novel genetic association of Wegener's granulomatosis with the interleukin 10 gene. J Rheumatol. 2002 Feb;29(2):317–320. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES