T-CELL HELPER TYPES AND ENDOCRINES IN THE REGULATION OF TISSUE-DAMAGING MECHANISMS IN TUBERCULOSIS

The necrotising immunopathology, which is accompanied by very little m ycobactericidal activity, is probably the key to the pathogenesis of t uberculosis. Conventional chemotherapy fails to correct this immunoreg ulatory anomaly, so the host response does little to assist the drugs in the removal of the ''persister'' subpopulation of bacteria. Therefo re chemotherapy must be prolonged for at least 6 months, with conseque nt problems of cost, resistance, and compliance. If we can learn to sw itch off the necrotising pathway, and replace it with bactericidal mec hanisms, treatment of the disease will be enormously improved and shor tened. One problem is that we do not know the mechanism oi cell-mediat ed immunity to tuberculosis in man. On the other hand, we are gaining some insights into the mechanism of the necrosis, and there are encour aging indications that it can indeed be separated from immunity, and t hat it can be suppressed by suitable immunotherapy. We present here so me evidence that when a TH2 response is superimposed upon a pie-existi ng TH1 response, the resulting cell-mediated inflammatory site becomes exquisitely sensitive to cytokine-mediated damage. There is clear evi dence for a TH2 component in the immune response of tuberculosis patie nts. This inappropriate TH1 to TH2 shift may result from subtle endocr inological changes brought about by M. tuberculosis and the response t o it. Immunotherapy should aim to switch off this TH2 component.