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Tuberculosis is characterised by fever, weight loss and necrosis in both lesions and tuberculin skin test sites (Koch phenomenon), although the antigens of Mycobacterium tuberculosis are not directly toxic to the tissues. The tissue damage appears to be due to several interacting factors. First, M. tuberculosis induces an immunoregulatory disorder of which a raised percentage of agalactosyl IgG is a marker. This is seen also in rheumatoid arthritis and Crohn’s disease and is associated with tissue-damaging inflammation. Subsequently, several properties of M. tuberculosis exacerbate this disorder by triggering cytokine release, and rendering tissues sensitive to the toxicity of tumor necrosis factor (TNF). Moreover, M. tuberculosis, but not bacillus Calmette-Guérin or several Mycobacterium avium strains, produces a factor which increases the toxicity of TNF for individual cells. Thus, M. tuberculosis may distort the normal protective role of TNF so that this cytokine becomes toxic to the host. The immunoregulatory disorder associated with agalactosyl IgG appears to be susceptible to immunotherapy, so novel types of treatment for the immunopathological component of tuberculosis are being explored.

No abstract

SUMMARYMycobacterial lesions and skin sites challenged with soluble mycobacterial antigen are very sensitive to the necrotizing effect of tumour necrosis factor (TNE). We have used a model that permits separate quantitative assessment of swelling and haemorrhage to show that when these reactions are elicited in mice that have not been deliberately immunized, pretreatment of the mice with lipopolysaccharide (LPS), or with a MoAb to CR3 which blocks emigration of myeloid cells into the tissues, will block both the swelling and the haemorrhage. On the other hand, treatment with an inhibitor of plateletactivating factor (PAE), or with misoprostol (a synthetic prostaglandin El analogue), or with cobra venom factor (CVE) which depletes complement, preferentially blocks the haemorrhagic component, while leaving the swelling relatively unaltered. As swelling occurs before the haemorrhage is seen, it is possible that these factors act at a late stage in the cascade of events leading to the tissue damage. However, LPS and CVF were able to inhibit swelling and haemorrhage in the massive reactions elicited in pre-immunized animals, whereas the PAE inhibitor had no detectable effect.