Tumour necrosis factor-alpha (TNF-α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions

Abstract

SUMMARY Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-α mRNA and TNF-α protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-α mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-α mRNA and TNF-α protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-α mRNA is more abundant than TNF-α protein; this may reflect the rapid turnover of TNF-α protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-α is generated as part of the host response to infection, but also produces local tissue damage.