02665nas a2200433   4500000000100000008004100001260006800042653001500110653001000125653001100135653001400146653002100160653003100181653001100212653001900223653002300242653002500265653000900290653001600299653000800315653005200323653001500375653001600390653001800406653001600424100001600440700001700456700001000473700001800483700001400501700001300515700001200528245012700540300001100667490000700678050001900685520151300704022001402217       2012                            d  c2012 MaybPhysicians Continuing Education CorporationaNew York10aAdolescent10aAdult10aBiopsy10aCytokines10aErythema Nodosum10aGene Expression Regulation10aHumans10aInterleukin-1710aLeprostatic Agents10aLeprosy, lepromatous10aMale10aMiddle Aged10aRNA10aReverse Transcriptase Polymerase Chain Reaction10aTh17 Cells10aThalidomide10aUp-Regulation10aYoung Adult1 aMartiniuk F1 aGiovinazzo J1 aTan A1 aShahidullah R1 aHaslett P1 aKaplan G1 aLevis W00aLessons of leprosy: the emergence of TH17 cytokines during type II reactions (ENL) is teaching us about T-cell plasticity.  a626-300 v11  aMARTINIUK 20123 a<p><b>BACKGROUND: </b>Leprosy was the first disease classified according to the thymus derived T-cell in the 1960s and the first disease classified by the cytokine profile as intact interferon-γ (IFN-γ) and interleukin-2 (IL2) or TH1 (tuberculoid) and deficient IFN-γ and IL2 or TH2 (lepromatous), in the 1980s.</p><p><b>OBJECTIVE: </b>In the present study, we set out to explore the T helper 17 (TH17) lymphocyte subset, the hallmark of T-cell plasticity, in skin biopsies from patients with erythema nodosum leprosum (ENL) who were treated with thalidomide.</p><p><b>METHOD: </b>RNA was extracted from paraffin embedded tissue before and after thalidomide treatment of ENL and RT-PCR was performed.</p><p><b>RESULTS: </b>IL17A, the hallmark of TH17, was consistently seen before and after thalidomide treatment, confirming the TH17 subset to be involved in ENL and potentially up-regulated by thalidomide.</p><p><b>CONCLUSION: </b>A reduction in CD70, GARP, IDO, IL17B (IL-20), and IL17E (IL-25), coupled with increases in RORγT, ARNT, FoxP3, and IL17C (IL-21) following thalidomide treatment, opens the door to understanding the complexity of the immunomodulatory drug thalidomide, which can operate as an anti-inflammatory while simultaneously stimulating cell-mediated immunity (CMI). We conclude that TH17 is involved in the immunopathogenesis of ENL and that thalidomide suppresses inflammatory components of TH17, while enhancing other components of TH17 that are potentially involved in CMI.</p>  a1545-9616