Reduction of chemokine secretion in response to mycobacteria in infliximab-treated patients

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 rheumat...

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Published in:Clinical and vaccine immunology Vol. 15; no. 3; p. 506
Main Authors: Newton, Sandra M, Mackie, Sarah L, Martineau, Adrian R, Wilkinson, Katalin A, Kampmann, Beate, Fisher, Corinne, Dutta, Shouma, Levin, Michael, Wilkinson, Robert J, Pasvol, Geoffrey
Format: Journal Article
Language:English
Published: United States 01.03.2008
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antirheumatic Agents - pharmacology
Antirheumatic Agents - therapeutic use
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - microbiology
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Assay
Chemokines - blood
Chemokines - drug effects
Down-Regulation
Humans
Infliximab
Luminescence
Middle Aged
Mycobacterium bovis - genetics
Mycobacterium bovis - metabolism
Spondylitis, Ankylosing - drug therapy
Spondylitis, Ankylosing - immunology
Spondylitis, Ankylosing - microbiology
Tuberculosis - immunology
Tuberculosis - microbiology
Tumor Necrosis Factor-alpha
ISSN:1556-679X, 1556-679X
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Summary: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-1alpha (MIP-1alpha), MIP-1beta (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-1beta 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.
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ISSN:1556-679X
1556-679X
DOI:10.1128/CVI.00401-07