Tumournecrosis factor-alpha (TNF-a)synthesis isassociated withtheskinand peripheral nervepathology ofleprosy reversal reactions

SUMMARY Leprosy may becomplicated byepisodes ofincreased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) whichresult inseverelocal immunopathology inskinlesions andperipheral nerves.Usinginsituhybridization andMoAb techniques we havedemonstrated TNF-amRNA andTNF-aprotein inmacrophages infiltrating leprosy skinandperipheral nerve. Levels ofTNF-amRNA aresignificantly increased inreactional skinandnerve,particularly in borderline tuberculoid patients. TNF-amRNA andTNF-aprotein levels arehigher inreactional nervesthenreactional skin. Inbothreactional skinandnerveTNF-amRNA ismore abundant thanTNF-aprotein; this may reflect therapid turnover ofTNF-aprotein inan immunologically dynamic situation, suchasisseeninreversal reaction. Ourfindings emphasize theimportance of documenting bothmRNA andprotein production whenassessing theroleofcytokines in pathology. Theleprosy reversal reaction may beregarded as a useful modeloftissue immunopathology inwhichTNF-aisgenerated aspartofthehost responsetoinfection, butalso produces local tissue damage.