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Immunology and Allergic Diseases

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Dubai, UAE
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Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis

Author(s): Nath N, Khan M, Paintlia MK, Singh I, Hoda MN, et al.

Abstract

Experimentalautoimmuneencephalomyelitis(EAE)isaTcell-mediatedautoimmunediseaseoftheCNS.MetforministhemostwidelyuseddrugfordiabetesandmediatesitsactionviaactivatingAMP-activatedproteinkinase(AMPK).WeprovideevidencethatmetforminattenuatestheinductionofEAEbyrestrictingtheinfiltrationofmononuclearcellsintotheCNS,down-regulatingtheexpressionofproinflammatorycytokines(IFN-gamma,TNF-alpha,IL-6,IL-17,andinducibleNOsynthase(iNOS)),celladhesionmolecules,matrixmetalloproteinase9,andchemokine(RANTES).Furthermore,theAMPKactivityandlipidsalterations(totalphospholipidsandinfreefattyacids)wererestoredbymetformintreatmentintheCNSoftreatedEAEanimals,suggestingthepossibleinvolvementofAMPK.MetforminactivatedAMPKinmacrophagesandtherebyinhibitedbiosynthesisofphospholipidsaswellasneutrallipidsandalsodown-regulatedtheexpressionofendotoxin(LPS)-inducedproinflammatorycytokinesandtheirmediators(iNOSandcyclooxygenase2).ItalsoattenuatedIFN-gammaandIL-17-inducediNOSandcyclooxygenase2expressioninRAW267.4cells,furthersupportingitsanti-inflammatoryproperty.MetformininhibitedTcell-mediatedimmuneresponsesincludingAg-specificrecallresponsesandproductionofTh1orTh17cytokines,whileitinducedthegenerationofIL-10inspleencellsoftreatedEAEanimals.Altogetherthesefindingsrevealthatmetforminmayhaveapossibletherapeuticvalueforthetreatmentofmultiplesclerosisandotherinflammatorydiseases.

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