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

SUMMARY Leprosy may be complicated by episodes of increased cell-mediated imtnunity tovk'ards Myco-bacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesionsand peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstratedTNF-a mRNA and TNF-o protein in macrophages infiltrating leprosy skin and peripheral nerve.Levels of TNF-Q mRNA are significantly increased in reactional skin and nerve, particularly inborderline tubercuioid patients. TNF-o mRNA and TNF-Q protein levels are higher in reactionalnerves then reactional skin. In both reactional skin and nerve TNF-a mRNA is more abundantthan TNF-a protein; this may reflect the rapid turnover of TNF-o protein in an immunologicallydynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance ofdocumenting both mRNA and protein production when assessing the role of eytokines inpathology. The leprosy reversal reaction may be regarded as a useful model of tissue immuno-patbology in which TNF-a is generated as part of the host response to infection, but also produceslocal tissue damage.Keywords leprosy reversal reaction TNF In situ hybridization nerve damage