title: T cell helper types and endocrines in the regulation of tissue-damaging mechanisms in tuberculosis.
abstract: The necrotising immunopathology, which is accompanied by very little mycobactericidal activity, is probably the key to the pathogenesis of tuberculosis. Conventional chemotherapy fails to correct this immunoregulatory anomaly, so the host response does little to assist the drugs in the removal of the "persister" subpopulation of bacteria. Therefore chemotherapy must be prolonged for at least 6 months, with consequent problems of cost, resistance, and compliance. If we can learn to switch off the necrotising pathway, and replace it with bactericidal mechanisms, treatment of the disease will be enormously improved and shortened. One problem is that we do not know the mechanism of cell-mediated immunity to tuberculosis in man. On the other hand, we are gaining some insights into the mechanism of the necrosis, and there are encouraging indications that it can indeed be separated from immunity, and that it can be suppressed by suitable immunotherapy. We present here some evidence that when a TH2 response is superimposed upon a pre-existing TH1 response, the resulting cell-mediated inflammatory site becomes exquisitely sensitive to cytokine-mediated damage. There is clear evidence for a TH2 component in the immune response of tuberculosis patients. This inappropriate TH1 to TH2 shift may result from subtle endocrinological changes brought about by M. tuberculosis and the response to it. Immunotherapy should aim to switch off this TH2 component.
authors.affiliation: Department of Medical Microbiology, UCL Medical School, London, England.
authors.forename: G A
authors.initials: GA
authors.lastname: Rook
authors.forename: R
authors.initials: R
authors.lastname: Hernandez-Pando
mesh_terms: D000311:Adrenal Glands / Q000503:physiopathology; D000818:Animals; D000942:Antigens, Bacterial; D002117:Calcitriol / Q000096:biosynthesis; D004702:Endocrine Glands / Q000503:physiopathology*; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D009336:Necrosis / Q000209:etiology; D012769:Shock / Q000209:etiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014376:Tuberculosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000633:toxicity; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol