Central European Journal of Immunology 2013; 38(1) 29 Experimentalimmunology Correspondence:GamalAllam,Currentaddress:DepartmentofMicrobiology,CollegeofMedicine,TaifUniversity,Taif,SaudiArabia; Permanent address: Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt, tel. +966 56 9288913, fax+96627250528,e-mail:g.allam@tu.edu.sa;gm_allam@yahoo.com Differential effect of hesperidin on Th1, Th2, Th17, and proinflammatory cytokines production from splenocyte of Schistosoma mansoni-infected mice GAMALALLAM 1,2 ,ABDELAZIZS.A.ABUELSAAD 1,2 1 DepartmentofMicrobiology,CollegeofMedicine,TaifUniversity,Taif,SaudiArabia 2 DepartmentofZoology,FacultyofScience,Beni-SuefUniversity,Beni-Suef,Egypt Abstract ThepresentstudywasconductedtoevaluatethepotentialeffectofhesperidinontheregulatingTh1, Th2,Th17,andtheproinflammatorycytokinesproductionfromsplenocyteofacutemurineschistoso- miasis.Eachmousewasinfectedwith100cercariaeof Schistosoma(S.)mansoni andat8weekspost- infection,miceweresacrificed,splenocyteswerepreparedandculturedinthepresenceofeithersolu- bleadultwormantigen(SWAP)orsolubleeggantigen(SEA)ofS.mansoniwitheither50or100 μM hesperidin. Hesperidin, in both tested concentrations, significantly augmented interleukin (IL) 4 (p<0.05),IL-10(p<0.01),andinterferon γ (IFN-γ)(p<0.05)productioninresponsetoSAWPand SEAstimulation.However,IL-13,IL-17,IL-1,andtumornecrosisfactor α (TNF-α)productionwere significantly(p<0.01)reduced.Interleukin12productionwasnotsignificantly(p>0.05)changedwith hesperidintreatmentat50 μM,while100 μMconcentrationofhesperidinsignificantlyreducedIL-12 productioninresponsetoSWAP(p<0.05)andSEA(p<0.01)stimulation.Theresultssuggestedthat hesperidinpreferentiallymodulatedinvitroproductionofTh1,Th2,Th17,andproinflammatorycytokines andthiscouldreduceimmunopathologyofschistosomiasis. Key words: hesperidin,schistosomiasis,Th1,Th2,Th17,proinflammatorycytokinesproduction. (CentrEurJImmunol2013;38(1):29-36) Introduction In Schistosoma (S.) mansoni infection,theoutcomeof theimmuneresponsedeterminesthebalancebetweenpro- tectiveimmunityandimmunopathology[1].Themorbid- ityin S.mansoni infectionarisesfromthegranulomatous responsetoeggsthatbecometrappedinthehosttissues withsubsequentfibrosis.Granulomaformationisdepend- entonCD4 + Tcellresponses[2,3],whileschistosomiasis isassociatedwithanimbalanceinThelper1(Th1)/Th2 cytokines[4].DifferentiationofCD4 + TcellsintoTh1or Th2lymphocytepopulationdependstoagreatextentupon therelativeabundanceofvariouscytokinesduringtheprim- ingoftheantigen-specificlymphocytepopulationbyanti- gen-presentingcells[5,6].Meanwhile,interleukin(IL)12 andIL-4,thekeypromotersofTh1andTh2cellpopula- tionsrespectively,botharemutuallyantagonistic.Inter- leukin4iscapableofinhibitingtheexpressionofthe β2 subunitoftheIL-12receptor[7]whileIL-12isresponsi- bleforthesuppressionofIL-4productioninainterferon γ (IFN-γ)-dependentmanner[8].Therefore,modulationof bothTh1andTh2responsescoulddownregulatethegran- ulomatousinflammationandconsequentlyreducemorbid- ityfromschistosomiasis. Inthecourseofaninfection,Th1responseisdominant inthefirst3-5weeksofinfectionduringthemigrationand thematurationofparasiteswhileTh2cytokineexpression becomes dominant shortly after egg laying begins; with IL-4, IL-5, IL-10, and IL-13 are the principal cytokines secretedbylymphoidcellsafterstimulationwithschisto- some egg antigens [9]. The secretion of Th1 cytokines, IFN-γ andIL-2,isconcurrentlydown-regulatedatthetime DOI:10.5114/ceji.2013.34355