title: Isoniazid (INH) treatment of INH-resistant Mycobacterium tuberculosis inhibits infected macrophage to produce TNF-alpha.
abstract: Macrophages undergo apoptosis after infected by Mycobacterium tuber- culosis (M.tb), which is regulated by tumor necrosis factor alpha (TNF-alpha) and has a direct correlation with killing of intracellular bacilli. In order to clarify the role of isoniazid (INH) in the modulation of macrophages apoptosis and intracellular bacilli replication, we performed the following studies using an INH-resistant clinical M.tb isolate (INHres). Macrophages derived from peripheral blood were infected with INHres and treated or not treated with INH. Apoptosis was measured using an Ag-capture ELISA for histone and fragmented DNA. Production of TNF-alpha by INHres infected was assayed using ELISA and viability of intracellular M.tb was determined using bacterial culture of macrophage lysates on Lowenstein-Jensen (LJ) medium. INH pre-treatment to INHres reduced macrophages apoptosis, production of TNF-alpha and intracellular INHres viability. This study indicated that INH affected TNF-alpha release resulting in reduction of the extent macrophages apoptosis and of intracellular INH-resistant M.tb viability.
authors.forename: Tri
authors.initials: T
authors.lastname: Wibawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Pangemanan
authors.forename: Farida J
authors.initials: FJ
authors.lastname: Rachmawaty
authors.forename: Ning
authors.initials: N
authors.lastname: Rintiswati
authors.lastname: Mustofa
authors.forename: Marsetyawan H N E
authors.initials: MH
authors.lastname: Soesatyo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009169:Mycobacterium tuberculosis; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid