Ann Rheum Dis 2001;60:750-755 ( August )

Extended report

Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNF D Baeten^a, N Van Damme^a, F Van den Bosch^a, E Kruithof^a, M De Vos^b, H Mielants^a, E M Veys^a, F De Keyser^a

^a Department of Rheumatology, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium, ^b Department of Gastroenterology

Correspondence to: Dr D Baeten dominique.baeten{at}rug.ac.be

Accepted for publication 17 November 2000

OBJECTIVESTo evaluate the effect of anti-TNF on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA).
METHODSPeripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN) were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry.
RESULTSAt baseline the percentage of T cells positive for IFN (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while IL10 (p=0.001) was increased. This cytokine profile, confirmed by the mean fluorescence intensities (MFI), was more pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK T cells, characterised by high IL4 and IL10 numbers, were also increased in patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFN and IL2 in patients with SpA. Moreover, there was a transient decrease in IL10 and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. This switch in cytokine profile was seen in both the CD3+/CD8- and CD3+/CD8+ subsets.
CONCLUSIONSBefore treatment patients with SpA had an impaired Th1 cytokine profile compared with healthy controls and patients with RA. TNF blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the effect of anti-TNF on the immune changes in SpA, and provide insights into the mechanisms involved in TNF blockade.

---

© 2001 by Annals of the Rheumatic Diseases
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Tsiodras, S., Samonis, G., Boumpas, D. T., Kontoyiannis, D. P. (2008). Fungal Infections Complicating Tumor Necrosis Factor {alpha} Blockade Therapy. Mayo Clin Proc. 83: 181-194 [Abstract] [Full Text]  
• Francois, R J, Neure, L, Sieper, J, Braun, J (2006). Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor {alpha} in two patients with early disease and transforming growth factor {beta} in three more advanced cases. Ann Rheum Dis 65: 713-720 [Abstract] [Full Text]  
• Duftner, C, Dejaco, C, Kullich, W, Klauser, A, Goldberger, C, Falkenbach, A, Schirmer, M (2006). Preferential type 1 chemokine receptors and cytokine production of CD28- T cells in ankylosing spondylitis. Ann Rheum Dis 65: 647-653 [Abstract] [Full Text]  
• Rihl, M, Gu, J, Baeten, D, Marker-Hermann, E, Goodall, J C, Gaston, J S H, Kuipers, J G, Zeidler, H, Yu, D T Y (2004). Alpha beta but not gamma delta T cell clones in synovial fluids of patients with reactive arthritis show active transcription of tumour necrosis factor {alpha} and interferon {gamma}. Ann Rheum Dis 63: 1673-1676 [Abstract] [Full Text]  
• Butrimiene, I., Jarmalaite, S., Ranceva, J., Venalis, A., Jasiuleviciute, L., Zvirbliene, A. (2004). Different cytokine profiles in patients with chronic and acute reactive arthritis. Rheumatology (Oxford) 43: 1300-1304 [Abstract] [Full Text]  
• Braun, J., Sieper, J. (2004). Biological therapies in the spondyloarthritides--the current state. Rheumatology (Oxford) 43: 1072-1084 [Abstract] [Full Text]  
• Nissinen, R, Leirisalo-Repo, M, Peltomaa, R, Palosuo, T, Vaarala, O (2004). Cytokine and chemokine receptor profile of peripheral blood mononuclear cells during treatment with infliximab in patients with active rheumatoid arthritis. Ann Rheum Dis 63: 681-687 [Abstract] [Full Text]  
• Stone, M A, Payne, U, Pacheco-Tena, C, Inman, R D (2004). Cytokine correlates of clinical response patterns to infliximab treatment of ankylosing spondylitis. Ann Rheum Dis 63: 84-87 [Abstract] [Full Text]  
• Jaakkola, E., Crane, A. M., Laiho, K., Herzberg, I., Sims, A.-M., Bradbury, L., Calin, A., Brophy, S., Kauppi, M., Kaarela, K., Wordsworth, B. P., Tuomilehto, J., Brown, M. A. (2004). The effect of transforming growth factor {beta}1 gene polymorphisms in ankylosing spondylitis. Rheumatology (Oxford) 43: 32-38 [Abstract] [Full Text]  
• Keller, C, Webb, A, Davis, J (2003). Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann Rheum Dis 62: 1128-1132 [Abstract] [Full Text]  
• Zou, J, Rudwaleit, M, Brandt, J, Thiel, A, Braun, J, Sieper, J (2003). Up regulation of the production of tumour necrosis factor {alpha} and interferon {gamma} by T cells in ankylosing spondylitis during treatment with etanercept. Ann Rheum Dis 62: 561-564 [Abstract] [Full Text]  
• van Roon, J A G, Bijlsma, J W J (2002). Th2 mediated regulation in RA and the spondyloarthropathies. Ann Rheum Dis 61: 951-954 [Full Text]  
• Khan, M A (2002). Ankylosing spondylitis: introductory comments on its diagnosis and treatment. Ann Rheum Dis 61: iii3-7 [Full Text]  
• Braun, J, Sieper, J, Breban, M, Collantes-Estevez, E, Davis, J, Inman, R, Marzo-Ortega, H, Mielants, H (2002). Anti-tumour necrosis factor {alpha} therapy for ankylosing spondylitis: international experience. Ann Rheum Dis 61: iii51-60 [Abstract] [Full Text]  
• Braun, J, Sieper, J (2002). Building consensus on nomenclature and disease classification for ankylosing spondylitis: results and discussion of a questionnaire prepared for the International Workshop on New Treatment Strategies in Ankylosing Spondylitis, Berlin, Germany, 18-19 January 2002. Ann Rheum Dis 61: iii61-67 [Abstract] [Full Text]  
• Van den Bosch, F, Baeten, D, Kruithof, E, De Keyser, F, Mielants, H, Veys, E M (2001). Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor alpha. Ann Rheum Dis 60: iii33-36 [Full Text]