ACTH The forgotten therapy 促肾上腺皮质激素治疗的遗忘.doc

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1、ELSEVIERSeminarsinCrossMarkContentslistsavailableatScienceDireciSeminarsinlmmunologyjournalhomepage:w*elsevici:com/loc

2、iversityofl.ondon,ChartcrhouseSquaraEC1M6BQ.London,UniledKingdomarticleinfoArLiclehistory:Received14January2015Received!nrevisedform7February2015Accepted9February2015Althoughanti-inflammalorydrugsarcamongthemostcommonclassofmarketeddrugschronicinflam-matorycondit

3、ionssuchasrheumatoidarthritismultiplesclerosisorinflammatoryboweldiseaserepresenlunmelnecds.Nowfirst-in-classdrugsmightbediscoveredinthefuturebutandfurtherdevelopmentofolddrugsalsoofferspromisefortheseconditions.ThisisstilltherepurposethecaseoftheKeywords:ACTHDru

4、gdiscoveiyGPCRInflammationMclanocortinPro-resolvingmediatorinelanocortinadrenocorticoiropinhormono,ACTH,usedinpatientssince1952butregardedasthelasttherapeuticoptionwhenothermedicationssuchasglucocorticoids>cannolbcuscd・Betterunderstand-ingonitsphvsiologicalandpha

5、rmacologicalmechanismsofactionsaminewinsightsonmclanocortinreceptorsbiologyhaverevivedtheinterestonrescuingthisoldandeffectivcdrug.ACTIIdoesnotonlyinducecortisolproductionfaspreviouslyassumed,butitalsoexertsanti-inflammatoryactionsbytarget-ingme!anocortinreceptor

6、spresentonimmunccellaThecndogenousagonistsf'orthesereceptors(ACTH,CZhLhandO-melanocytestimulatinghormones),arealsoproducedlocallybyimmunecellsindicatingthcexisteneeofanendogenousanii-inflammalorytissue-protectivecircuitinvolvingthemelanocortinsyslem.Thesefiriding

7、ssuggeslcdlhalriewACTIl-likemelAnocorlindrugsdcvoidofsleroidogenicaction%andhencosidecffeclscouldbedeveloped・ThisreviewsuinmarizestheadionsofACTHandmelanocortindrugs,theirroleasendogenouspro-resolvingmcdiatorstheircurrentclinicaluseandprovidesanoverviewonhowrecen

8、iadvancesonGPCRfunctioningmayleadloanovelclassofdrugs.^20IoKlscvierl.idAllrightsreserved1.IiiltoduclionDoweneednewdrugstoLreathumandiseases?Doweneednovellherap