Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. Export

@article{citeulike:2897521, abstract = {Tumor necrosis factor (TNF) is a prototypic proinflammatory cytokine that contributes significantly to the development of immunopathology in various disease states. A complication of TNF blockade therapy, which is used increasingly for the treatment of chronic inflammatory diseases, is the reactivation of latent tuberculosis. This study used a low-dose aerogenic model of murine tuberculosis to analyze the effect of TNF neutralization on disease progression in mice with chronic tuberculous infections. Histological, immunohistochemical, and flow cytometric analyses of Mycobacterium tuberculosis-infected lung tissues revealed that the neutralization of TNF results in marked disorganization of the tuberculous granuloma, as demonstrated by the dissolution of the previously described B-cell-macrophage unit in granulomatous tissues as well as by increased inflammatory cell infiltration. Quantitative gene expression studies using laser capture microdissected granulomatous lung tissues revealed that TNF blockade in mice chronically infected with M. tuberculosis leads to the enhanced expression of specific proinflammatory molecules. Collectively, these studies have provided evidence suggesting that in the chronic phase of M. tuberculosis infection, TNF is essential for maintaining the structure of the tuberculous granuloma and may regulate the granulomatous response by exerting an anti-inflammatory effect through modulation of the expression of proinflammatory mediators.}, address = {Department of Medicine and Microbiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, F406, Bronx, NY 10461, USA.}, author = {Chakravarty, S. D. and Zhu, G. and Tsai, M. C. and Mohan, V. P. and Marino, S. and Kirschner, D. E. and Huang, L. and Flynn, J. and Chan, J.}, citeulike-article-id = {2897521}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/IAI.01011-07}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18212087}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18212087}, doi = {10.1128/IAI.01011-07}, issn = {1098-5522}, journal = {Infection and immunity}, keywords = {granuloma, mouse, mycobacterium\_tuberculosis, tnf}, month = {March}, number = {3}, pages = {916--926}, posted-at = {2008-06-16 05:08:46}, priority = {0}, title = {Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs.}, url = {http://dx.doi.org/10.1128/IAI.01011-07}, volume = {76}, year = {2008} }

TY - JOUR ID - citeulike:2897521 L3 - citeulike-article-id:2897521 N2 - Tumor necrosis factor (TNF) is a prototypic proinflammatory cytokine that contributes significantly to the development of immunopathology in various disease states. A complication of TNF blockade therapy, which is used increasingly for the treatment of chronic inflammatory diseases, is the reactivation of latent tuberculosis. This study used a low-dose aerogenic model of murine tuberculosis to analyze the effect of TNF neutralization on disease progression in mice with chronic tuberculous infections. Histological, immunohistochemical, and flow cytometric analyses of Mycobacterium tuberculosis-infected lung tissues revealed that the neutralization of TNF results in marked disorganization of the tuberculous granuloma, as demonstrated by the dissolution of the previously described B-cell-macrophage unit in granulomatous tissues as well as by increased inflammatory cell infiltration. Quantitative gene expression studies using laser capture microdissected granulomatous lung tissues revealed that TNF blockade in mice chronically infected with M. tuberculosis leads to the enhanced expression of specific proinflammatory molecules. Collectively, these studies have provided evidence suggesting that in the chronic phase of M. tuberculosis infection, TNF is essential for maintaining the structure of the tuberculous granuloma and may regulate the granulomatous response by exerting an anti-inflammatory effect through modulation of the expression of proinflammatory mediators. IS - 3 JF - Infection and immunity SN - 1098-5522 AD - Department of Medicine and Microbiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, F406, Bronx, NY 10461, USA. EP - 926 TI - Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. VL - 76 SP - 916 KW - granuloma KW - mouse KW - mycobacterium_tuberculosis KW - tnf AU - Chakravarty, SD AU - Zhu, G AU - Tsai, MC AU - Mohan, VP AU - Marino, S AU - Kirschner, DE AU - Huang, L AU - Flynn, J AU - Chan, J PY - 2008/03// UR - http://dx.doi.org/10.1128/IAI.01011-07 ER -