title: Effects of isoniazid (INH) on the BCG-induced local immune response after intravesical BCG therapy for superficial bladder cancer.
abstract: Because recent investigations showed that the use of isoniazid (INH) severely impaired the local immune reaction to intravesical bacillus Calmette-Guérin (BCG) in the bladder of guinea pigs, in this study the effect of INH in man has been investigated. Patients were treated with BCG with or without oral INH. The concentration of free INH in most urine samples of patients treated with BCG/INH was much higher (mean 38.0 +/- 60.9 micrograms INH/ml) than the minimal inhibitory concentration (MIC; 0.1 microgram INH/ml), suggesting at least a bacteriostatic potential of the INH present. However, in vitro studies showed that these urinary concentrations of INH did not kill BCG organisms effectively, even at a concentration of 150 micrograms/ml for 24 h. After the fifth and sixth BCG instillations a significant increase in the concentration of cytokines (IL2, IL6, IL8 and TNFa), IgG and IgA antibodies to BCG and the number of leukocytes in urine was observed. The leukocytes mainly consisted of granulocytes, besides monocytes/macrophages and, in lower amounts, T- and B-lymphocytes and natural killer (NK) cells. The absolute number of granulocytes and the concentration of IgG antibodies after BCG instillation were significantly suppressed by INH, whereas INH appeared to have no effect on the urinary cytokine and IgA antibody concentrations or the total number and phenotype of the leukocytes present. In conclusion, the results of this study indicate that INH does not impair the local immunological stimulation after BCG instillation in man as severely as was observed in the guinea pig and it may be expected that INH does not impair the antitumor efficacy of BCG.
authors.affiliation: Laboratory for Pathology, National Institute of Public Health and Environmental Protection (RIVM), Bilthoven, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Stassar
authors.forename: P D
authors.initials: PD
authors.lastname: Vegt
authors.forename: P A
authors.initials: PA
authors.lastname: Steerenberg
authors.forename: A P
authors.initials: AP
authors.lastname: van der Meijden
authors.forename: H D
authors.initials: HD
authors.lastname: Meiring
authors.forename: M
authors.initials: M
authors.lastname: Dessens-Kroon
authors.forename: H G
authors.initials: HG
authors.lastname: Geertzen
authors.forename: W
authors.initials: W
authors.lastname: den Otter
mesh_terms: D000283:Administration, Intravesical; D000907:Antibodies, Bacterial / Q000032:analysis; D000917:Antibody Formation / Q000187:drug effects; D002452:Cell Count; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy; D007378:Interleukins / Q000652:urine; D007538:Isoniazid / Q000627:therapeutic use* / Q000652:urine; D007962:Leukocytes / Q000145:classification / Q000187:drug effects; D009163:Mycobacterium bovis / Q000276:immunology* / Q000502:physiology; D009994:Osmolar Concentration; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000652:urine; D014556:Urine / Q000166:cytology
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid