02690nas a2200337   4500000000100000008004100001260001600042653001800058653001400076653003000090653002000120653001100140653001200151653001600163653002800179653003000207653003000237653001900267100001500286700001300301700001400314700001400328700001200342700001400354700001500368245006500383300001100448490000800459520187100467022001402338       1992                            d  c1992 Aug 1510aBase Sequence10aCytokines10aCytotoxicity, Immunologic10aGene Expression10aHumans10aleprosy10aLymphokines10aMolecular Sequence Data10aOligodeoxyribonucleotides10apolymerase chain reaction10aRNA, Messenger1 aYamamura M1 aWang X H1 aOhmen J D1 aUyemura K1 aRea T H1 aBloom B R1 aModlin R L00aCytokine patterns of immunologically mediated tissue damage.  a1470-50 v1493 a<p>Reactional states in leprosy are produced by different immunologic mechanisms and are responsible for a major component of tissue damage of the disease. Reversal reactions exhibit increased CD4 T cell infiltration in lesions and augmented cell-mediated immune reactivity to Ag of Mycobacterium leprae that can rapidly produce nerve damage. Erythema nodosum leprosum (ENL) reactions also have CD4 T cell infiltration but appear to be associated with the formation of immune complexes that are responsible for panniculitis, arthritis, vasculitis, and nerve injury. Because these reactional states may serve as paradigms for other types of human immunologically mediated tissue damage, this study sought to characterize the dynamic changes in cytokines associated with these reactions. Expression of cytokine mRNA in lesions of leprosy reactional states were measured by PCR. In reversal reactions, IL-1 beta, TNF-alpha, IL-2, and IFN-gamma mRNA were prominent and found to increase during the reaction, concomitant with decreases in expression of mRNA for IL-4, IL-5, and IL-10. In ENL, selective increases in the expression of IL-6, IL-8, and IL-10 mRNA was observed, with persistent expression of IL-4 and IL-5 mRNA. Reversal reactions represent naturally occurring delayed-type hypersensitivity reactions that favor macrophage activation and protective immunity, but which can engender concomitant cell injury. In contrast, ENL lesions represent immediate-type hypersensitivity reactions reflecting the selective stimulation of cytokines that attract neutrophils, stimulate antibody production, and down-regulate macrophage activation. The analysis of cytokine dynamics within different inflammatory responses can provide insights into immune mechanisms of tissue damage, and provide a useful framework for developing strategies for therapeutic intervention.</p>  a0022-1767