This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Newton, S. M.
Right arrow Articles by Pasvol, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Newton, S. M.
Right arrow Articles by Pasvol, G.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, March 2008, p. 506-512, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00401-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Reduction of Chemokine Secretion in Response to Mycobacteria in Infliximab-Treated Patients{triangledown}

Sandra M. Newton,1 Sarah L. Mackie,2,{dagger} Adrian R. Martineau,1 Katalin A. Wilkinson,1,{ddagger} Beate Kampmann,1 Corinne Fisher,2,§ Shouma Dutta,2 Michael Levin,1 Robert J. Wilkinson,1,{ddagger} and Geoffrey Pasvol1*

Wellcome Trust Centre for Clinical Tropical Medicine and Department of Paediatrics, Imperial College London, Wright Fleming Institute, Norfolk Place, London W2 1PG,1 Rheumatology Department, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ, United Kingdom2

Received 3 October 2007/ Returned for modification 29 November 2007/ Accepted 14 December 2007

The use of anti-tumor necrosis factor (TNF) agents as a treatment for chronic inflammatory conditions has been shown to be associated with an increased risk of developing tuberculosis. We studied the effect of the anti-TNF antibody infliximab on antimycobacterial immunity in 26 patients with rheumatoid arthritis or ankylosing spondylitis by use of an in vitro whole-blood model employing a reporter mycobacterium. Blood samples taken before and 30 min and 7 days after a 2-hour infliximab infusion were compared in terms of their abilities both to suppress luminescence of Mycobacterium bovis bacillus Calmette-Guérin lux and to secrete chemokines and cytokines 24 and 96 h after infection. No immediate effect of infliximab on mycobacterial luminescence was detected using this bioassay, irrespective of whether patients were receiving their first (n = 14) or maintenance (n = 12) doses of infliximab. Moreover, no effect on mycobacterial luminescence was detected when blood was taken 7 days after infliximab treatment (n = 7). By contrast, there was a significant reduction in the chemokines implicated in cellular trafficking, namely, interleukin-8, macrophage-inhibitory protein-1{alpha} (MIP-1{alpha}), MIP-1β (24 h and 96 h), and monocyte chemoattractant protein-1 (MCP-1) (24 h) following BCG lux strain infection in the 30-minute post-infliximab-infusion blood samples (P < 0.05). This effect was sustained by MIP-1β and MCP-1 (24 h; P < 0.05) at 7 days after infusion. Our results suggest that the development of tuberculosis in infliximab-treated patients is not directly related to the mycobactericidal effects of TNF but may be due to inhibition of TNF-dependent chemokine gradients disrupting cellular migration necessary to maintain the integrity of the granuloma.

* Corresponding author. Mailing address: Department of Infection and Tropical Medicine, Imperial College London, Lister Unit, Northwick Park Hospital, Middlesex HA1 3UJ, United Kingdom. Phone: 44 (0)20 8869 2831. Fax: 44 (0)20 8869 2836. E-mail: g.pasvol{at}imperial.ac.uk

{triangledown} Published ahead of print on 26 December 2007.

{dagger} Present address: Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, United Kingdom.

{ddagger} Present address: Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.

§ Present address: Rheumatology Department, University College Hospital, London NW1 2PQ, United Kingdom.

Clinical and Vaccine Immunology, March 2008, p. 506-512, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00401-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»