PMID- 18160618 OWN - NLM STAT- MEDLINE DCOM- 20080416 LR - 20220227 IS - 1556-679X (Electronic) IS - 1556-6811 (Print) IS - 1556-679X (Linking) VI - 15 IP - 3 DP - 2008 Mar TI - Reduction of chemokine secretion in response to mycobacteria in infliximab-treated patients. PG - 506-12 AB - 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-Guerin 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. FAU - Newton, Sandra M AU - Newton SM AD - Wellcome Trust Centre for Clinical Tropical Medicine and Department of Paediatrics, Imperial College London, Wright Fleming Institute, United Kingdom. FAU - Mackie, Sarah L AU - Mackie SL FAU - Martineau, Adrian R AU - Martineau AR FAU - Wilkinson, Katalin A AU - Wilkinson KA FAU - Kampmann, Beate AU - Kampmann B FAU - Fisher, Corinne AU - Fisher C FAU - Dutta, Shouma AU - Dutta S FAU - Levin, Michael AU - Levin M FAU - Wilkinson, Robert J AU - Wilkinson RJ FAU - Pasvol, Geoffrey AU - Pasvol G LA - eng GR - GR077273MA/WT_/Wellcome Trust/United Kingdom GR - 060079/WT_/Wellcome Trust/United Kingdom GR - 077273/WT_/Wellcome Trust/United Kingdom GR - 064261/WT_/Wellcome Trust/United Kingdom GR - MC_U117588499/MRC_/Medical Research Council/United Kingdom GR - 072070/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071226 PL - United States TA - Clin Vaccine Immunol JT - Clinical and vaccine immunology : CVI JID - 101252125 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antirheumatic Agents) RN - 0 (Bacterial Proteins) RN - 0 (Chemokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - B72HH48FLU (Infliximab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/pharmacology/*therapeutic use MH - Antirheumatic Agents/pharmacology/therapeutic use MH - Arthritis, Rheumatoid/*drug therapy/immunology/microbiology MH - Bacterial Proteins/genetics/metabolism MH - Biological Assay MH - Chemokines/*blood/drug effects MH - *Down-Regulation MH - Humans MH - Infliximab MH - Luminescence MH - Middle Aged MH - Mycobacterium bovis/genetics/*metabolism MH - Spondylitis, Ankylosing/*drug therapy/immunology/microbiology MH - Tuberculosis/immunology/microbiology MH - Tumor Necrosis Factor-alpha PMC - PMC2268261 EDAT- 2007/12/28 09:00 MHDA- 2008/04/17 09:00 PMCR- 2008/09/01 CRDT- 2007/12/28 09:00 PHST- 2007/12/28 09:00 [pubmed] PHST- 2008/04/17 09:00 [medline] PHST- 2007/12/28 09:00 [entrez] PHST- 2008/09/01 00:00 [pmc-release] AID - CVI.00401-07 [pii] AID - 0401-07 [pii] AID - 10.1128/CVI.00401-07 [doi] PST - ppublish SO - Clin Vaccine Immunol. 2008 Mar;15(3):506-12. doi: 10.1128/CVI.00401-07. Epub 2007 Dec 26.