Comparative Assessment of the Cytokine Profile in Dynamics in Patients with Orthopedic Constructions from Different
Construction Materials
Otabekrajabov1,Zaynitdinkamalov2,Husnitdinirsaliev3,Fatimairsalieva4 1 - Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan.
2 - InstituteofImmunologyandgenomicsofhumanAcademySciences,RepublicofUzbekistan.
3 - Tashkent State Dental Institute 4 - TashkentMedicalAcademy
ABSTRACT
Thestateofthefactorsoflocalimmunityoftheoralcavityintheoralfluidbeforeandafterprostheti cswiththeuseoffixedstructuresmadeofcermetandzirconiummaterialswasstudiedin180peopleaged2 0-
70yearsand30practicallyhealthypeopleinthecomparisongroupofthesameage.Theoralfluiddetermin edandreferringlevelsofproinflammatorycytokinesIL-1β,IL-6,FNO-αandanti-
inflammatorycytokineIL-
10.Itwaswellestablishedand(straight)dependingsstateofimmunehomeostasis(cytokinestatus)oralm ucosaofmaterialorthodonticsecondstructure.
KEY WORDS:homeostasis,oralfluid,interleukins,tumornecrosisfactor,orthopedic
INTRODUCTION
Morethan70%ofthepopulationofourRepublicattheageof20- 60hasaviolationoftheintegrityofthedentition-
andtheneedfororthopedicdentaltreatment.AccordingtotheWHOcurrentlyupto75%ofpopulationinv ariousregionsoftheworldsufferfrompartialabsenceofteeth[3,12].Defectsinthedentitionareawidespr eadpathologyofthedentoalveolarsystem;theneedfororthopedictreatmentwithprosthesesis33–
58%[6].
Theproblemoftherelationshipbetweenthetissuesoftheoralcavityandvariousprostheticstructu resandmaterialsisthemainoneintheclinicoforthopedicdentistry,therefore,muchattentionispaidtoit,b othindomesticandforeignliterature[7,12,13].
Metal-
ceramicprosthesesarestructuresthatrepresentaframe,thebaseofwhichismadeofmetal,theuppercoati ngismadeofceramics.Today,metal-
ceramicprostheticsarethemostdemandedamongpatients.Thisisduetothemanyadvantagesthatmetal- ceramicstructureshave[8,13].
Orthopediczirconiumconstructionsaremadeofzirconiumdioxide.Forprosthetics,notapuremi neralisused,butamaterialwithadditivesofitriumandaluminum.Duetothenaturalpropertiesofthebase materialandadditives,dentalzirconiumishighlyresistanttovariousexternalfactorsandmechanicalstre ss.Animportantqualityisthehypoallergenicofzirconium,whichmeansthatdentalprosthesesmadeofth ismaterialareabsolutelyharmlessandcanbeusedtorestoreteethandinpeoplewithindividualintoleranc etometals[2,5,12].
Thebiologicalcompatibilityofadentureisdeterminedbyitseffectonthesurroundingtissuesand physiologicalprocessesintheoralcavity,andisdeterminedbyanumberoffactors:mechanical(thedesig
noftheprosthesis),chemical(thereleaseofresidualtoxicmonomer),physical(hyperthermia),biologica l,etc.Allofthemcausepathologicalchangesinperiodontaltissues.Pathologyofthemucousmembraneu ndertheprosthesismaybetheresultofanimbalancebetweenthemechanismsofaggressionanddefense[7 ].
Inmodernstudies,theleadingroleofcytokinesinthedevelopmentoftheinflammatoryresponseo ftheoralcavityduringadaptationtoprosthesesthatinitiatealocalimmuneresponseisalsoshown[4,10].
Recentstudiesprovethatthecontentofcytokinesinsalivadoesnotcorrelatewiththeirlevelintheb lood,whichindicatesacertainautonomyofthelocalimmunityoftheoralcavityandatthesametimereflect sthegeneraltendenciesofthecytokinecascadeinthepatient'sbody.Thiscorrespondstotheideathatsaliv arycriteriareflectnotonlylocal,butalsogeneraldisordersofhomeostasis[1].
Accordingtotheabove,thepurposeofthisstudywastosubstantiatethechoiceofmaterialforortho pedicstructuresbasedonacomparativeassessmentofcytokinestatusindicatorscharacterizingthestateo fimmunehomeostasisoftheoralmucosa(OOM)afterprosthetics.
MATERIALS AND METHODS
Immunologicalstudieswerecarriedoutinthelaboratoryofimmunoregulationoftheinstituteoft heImmunologyandHumanGenomicsofAcademyofSciencesoftheRepublicofUzbekistan.Thestudyi nvolved180patients(115womenand65men),aged20to70yearsold.Theaverageageofwomenwas38y earsold,men-49yearsold.Thepatientswereconditionallydividedintotwogroups:
1stgroup-180patients(115womenand65men)whounderwentmetal-ceramicprosthetics;
Group2-30healthypatients(17womenand13men)whounderwentzirconiumprosthetics.
Thecontrolwasthedataofasurveyof30apparentlyhealthyvolunteers,comparableinageandsex .
MeasurementofconcentrationofIL-1β,IL-6,IL-
10,TNFαinoralliquid(GC),wasconductedbyenzymeimmunoassay(ELISA)usingcommercialkitsA O"Vector-
Best".Gastrointestinaltractsamplingwasperformedbeforecomplextreatmentinpatientswithdefectsin dentitionandharddentaltissuesandafterprosthetics,notearlierthanafter30days,aswellasinhealthyindi viduals.Todothis,atthedentalappointment,thepatientwasaskedtorinsetheoralcavitywith3smallvolu mesofplainwaterandthinkaboutlemontostimulatesalivation.Sterilepenicillinvialswithavolumeof10 mlwereusedastesttubes,whichpatientsfilledwiththeirgastriccancerupto1/3-
1/2ofthetotalvolume.Thenglassvialswiththetestmaterialwerefrozeninafreezerandstoredatminus20°
Cfornomorethanonemonth.Thereafter,undilutedsampleswerethawedveryquicklybyheattreatmenti nawaterbathat37°Ctopreventfibrinogenprecipitation.
ThedatawerestatisticallyprocessedusingtheStatistics6.0computerprogram.Thereliabilityof differencesinthemeanvaluesofthecomparedindicatorswasassessedbytheStudent'stest(t).
RESULTS AND DISCUSSION
Thedevelopmentofinflammatorydiseasesisdeterminedbythestateofcytokineregulation.Mos tofbothpro-andanti-
inflammatorycytokinesarepresentnotonlyintheperipheralblood,butalsoinotherbiologicalfluidsofth ebody[9].Thesourcesoftheirproductionarebothlymphocytesandmacrophagesbuiltintotheepitheliu mofthemucousmembranes,andtheepithelialcellsofthemucousmembranesandthesalivaryglandsthe mselves.Anothersourceofcytokinesingastriccancer(saliva)maybetheirextravasationfrombloodseru
m.However,manyresearchershavenotedthatthecontentofcytokinesingastriccancer(saliva)doesnotc orrelatewiththeirlevelintheblood,whichindirectlyindicatestheirlocalsynthesis[11].
AccordingholdingmuanalysisinaGCpatientsandofhealthyindividualswereidentifiedsignific antdifferencesinthecontentofthetestofpro-inflammatoryIL-1β,IL-6,FNO-αandanti-IL-
10cytokines(Table.1).
Table1.Thelevelofpro-andanti-
inflammatorysxcytokinesintheoralfluidofpatientsstudiedbeforebeginningprosthetic(Mm,p g/ml)
n IL-1β IL-6 TNF-α IL-10
Main(general)group 180 7.5±0.20* 14.7±0.46* 12.3±0.32* 106±0,32*
Controlgroup thirty 4.2±0.26 11.8±0.55 9.4±0.39 8.5±0,38 Note:*Valuesarereliableinrelationtothedataofthecontrolgroup(P<0.05-0.001)
AnalysisofthedatasetthatthecontentofIL-
1βtotreatpatientswasaboutinthemiddle7,5±0,20pg/ml,thenlikethecomparisongroup,itsconcentratio nwas4.2±0.26pg/ml(P<0.001).TheconcentrationofIL-
6inthegeneralgroupofpatientsbeforethestartoforthopedictreatmentexceededthevaluesofthecontrol groupbymorethan1.3times(14.7±0.46pg/mlversus11.8±0.55,pg/ml,P<0.001),whichindicatesanalr eadyformedinflammatoryfocusintheoralcavity.
Asarule,thecontentofFNO-
αisnotdetermined,orisatalowlevelinthebloodserumofhealthypeople,whereaswiththedevelopmento fapathologicalprocess,itsamountincreasesseveraltimes.Thus,synthesisFNO-
αinpatientswiththegrouptoprostheticaveraged12.3±0.32pg/ml,andthesevalueswereinthecontrolgro up9.4±0.39pg/ml,whichis1.3timesmore(P<0.001).Itwasalsofoundthatasignificantincreaseinthelev elofIL-
10inthemainobservationgroupbeforeorthodontictreatmentwas1.2times(10.6±0.32pg/mlversus8.5±
0.38pg/ml)(P<0.001).
Theobtaineddatawithcytokinestatusoftheoralcavitybeforetheprostheticspointtotheweakeni ngofthelocalimmunedefenseGPRS,connectivitywiththeneedfortheorthopedicintervention.
Aftertheimpositionofdentures,the1stdentalexaminationwascarriedoutthenextday,atthestag eofdenturecorrection.Treatmentofinflammatorychangesinthemucousmembranewascarriedoutboth atthereceptionandathomeusingpreparationscontainingantiseptic,anesthetic,regeneratingcomponen tsinaccordancewiththe"Protocolforthemanagementofpatientswithpartialabsenceofteeth(partialsec ondaryadentia)".
Thus,intheI-
groupCeramicprosthesesafter7days,83%(72)patientscomplainedofpainintheoralmucosaduringinte rdigitationanduponapplicationofthedenture.Examinationrevealedinflammatorychangesinthemuco usmembraneoftheprostheticbed,whichwererepresentedbyhyperemiaanderosion,localizedintheregi onoftheborderofthedenture,aswellasinareasofincreasedbasepressureonthemucousmembrane.Atthe repeatedstagesofthedenturecorrection,thepatientsshowednocomplaints,noinflammatorychangesw erefoundontheoralmucosa.
Thestudyofthecontentofcytokinesshowedthatinpatientswithreddeningofthemucousmembr ane,theareaofwhichcoincidedwiththeshapeoftheedgeofthemetal-
ceramicdenture,alreadyonthe7thday,acytokineimbalancewasnotedintheoralfluid,characterizedbya significantincreaseinthecontentofIL-1β,IL-6,IL-10,andFNO-α(Fig.1).
ComparativeanalysisofthecontentrevealedthatingroupIwithmetal- ceramicprosthetics,thelevelofIL-
1βincreasedby3timesafteraweekwithanaveragevalueof22.7±0.35pg/ml(beforetreatment,7.5±0.20 pg/ml)(P<0.001),theconcentrationofIL-
6increasedto42.9±1.07pg/ml(beforetreatment14.7±0.46pg/ml)(P<0.001),TNF-α- 37.2±0.76pg/ml(beforetreatment12.3±0.32pg/ml)(P<0.001),IL-10-
215±0,55pg/ml(beforetreatment10.6±0.32pg/ml)(P<0.001)(Fig.1).
ThecytokineprofileoforalmucosaafteraweekinpatientsofgroupIIwithzirconiumprosthesessi gnificantlydifferedfromthegroupwithmetal-
ceramicprosthetics.Whenexaminingtheoralcavityin91%(84)ofpatientswithzirconiumprostheticsal readyafter7days,thetightfitofthezirconiumprosthesestothetissuesoftheoralcavityexcludedsubsiden ceofthegums,exposureofthedentalroot,andinflammationofthesofttissuesoftheoralcavity(Fig.2).
SothecontentofIL-
1βafteraweekingroupIIaveragedabout19.4±0.61pg/ml(P<0.001),theconcentrationofFNO-
αsignificantlyreachedapeakafter7days28.5±1,04pg/ml(P<0.001),thecontentafter7dayswas34.2±0.
62pg/ml(P<0.001),inpatientsaftertheinstallationofanorthopedicconstruction,thelevelofIL- 10increasedonaverageto16.7±0.57pg/mlafter7days(P<0.001)(Fig.2).
Fig.1Thecontentofcytokinesinthegastriccan cerafterprostheticsafter7and30daysinpatie
ntswithmetal-ceramicprostheses
Fig.2.Contentofcytokinesingastriccancerafter prostheticsafter7and30daysinpatientswithzir
conprostheses
Thestudyofthedynamicsoftheabovementionedmediatorsofinflammationrecordedadecrease intheexpressionwith30daysafterfixationofthefixedbridge,butthesedatadidnotreachthevaluesbefore thestartoftreatmentanddidnotundergosignificantfluctuationsinthefuture,thatis,remainedwithinthes pecifiedconcentrations.
Thus,ingroupIofpatientswithmetal-ceramicprostheticsafter1month,thelevelofIL- 1βdecreasedto16.4±0.74pg/ml(P<0.001),IL-6to28.7±0.72pg/ml(P<0.001),TNF-α- 24.5±1.03pg/ml(P<0.001),IL-10-15.3±0.65pg/ml(P<0.001)(Fig.1).
ItisimportanttonotethatintheIIgroupofpatientswithzirconiumprosthetics,thelevelofIL- 1βafteramonthofprostheticimplantationretainedatendencytodecreaseby30%comparedtothevaluesa fter7days.Thus,thecontentofIL-1βafter30daysis13.6±0.46pg/ml(P<0.001).(Fig.2.)
0 20 40 60
IL-1β IL-6 FHO-α IL-10 22.7
42.9 37.2
16.4 21.5
28.7 24.5
15.3
Sintered metal
after 7 days after 30 days
0 20 40
IL-1β IL-6 FHO-α IL-10 19.4
34.2
28.5 13.6 16.7
24.5
14.8 12.3
Zirconium
after 7 days after 30 days
ConcentrationofFNO-
αwassignificantlydecreasedonDay30to14.8±0.36pg/ml,butdidnotreachtheinitialvalues(starting- 12.3±0,32pg/ml(P<0.05).Theratingofcontentvia1monthestablishedaslightdecreaseintheexpression ofIL-6to24.5±1.03pg/ml(P<0.001).Adeclineafter1monthwasobservedinthelevelofIL-
10,whichaveraged12.5±0.68pg/ml(P<0.001)(Fig.2.)
Theseindicatorsindicateadecreaseintheinflammatoryresponseoftheoralcavity,albeitslow,bu tstabilizationofthelocalimmunemoodoftheoralcavity.
Therevealedsignificantincreaseintheconcentrationofpro-inflammatorycytokinesIL- 6andTNF-αafter7daysand1monthinbothgroupsindicatesasignificantdecreaseinanti-
infectiousresistanceintheoralcavity,whichisaconsequenceofanimbalancebetweenthenormalfloraan dthebody'simmuneresponseatthelocallevel.
Thus,onthebasisofthestudiescarriedout,itcanbestatedthattheestablishedcytokineimbalancei ngastriccanceringroupIwithmetal-
ceramicprostheticsindicatesanincreaseintheantigenicloadandanincreaseinthepermeabilityoftheora lmucosaasaresultofatraumaticgenesoprostheticbedand,asaconsequenceofthedevelopedinflammato ryprocess,whichohcausesdiscomfort.
ComparativeanalysisoftheobtaineddataofgroupIIwithzirconiumprostheticsrevealedapositi
ve dynamic of
indicesoflocalimmunitylinksingastriccancerinpatientsofthisgroup.Onexamination,nofociofinflam mationcausedbytheprostheseswereobserved,whichindicatesasatisfactoryregenerationofthetissueso ftheprostheticbed,andaccordingtothepatients,theywerecompletelyadaptedtothedenture.
Theobtaineddataofthecomparativeanalysismakeitpossibletodevelopanalgorithmforthetreat mentoftheconsequencesofmetal-
ceramicandzirconiumprostheses,intheuseoforthopedicstructuresmadeofvariousmaterials.
CONCLUSION
1.Theactivationoftheinflammatoryprocessintheperiodontaltissueswasestablished,manifest edbyanincreaseintheconcentrationofpro-andanti-
inflammatorycytokinesalreadyonthe7thdayafterfixationoftheprostheticstructure.
2.Itwasrevealedthatwithzirconiumprosthetics,thepositivedynamicsofindicesoflocalimmuni tylinksingastriccancerinpatientsofthisgroup.Onexamination,nofociofinflammationcausedbythepr ostheseswereobserved,whichindicatesasatisfactoryregenerationofthetissuesoftheprostheticbed,an dinthepatients'opinion,theywerecompletelyadaptedtothedenture.
ACKNOWLEDGEMENTS
We are grateful to the staff members of Bukhara State Medical Institute named after Abu Ali ibn Sino, Institute of Immunology and genomics of human Academy Sciences, Tashkent State Dental Institute and Tashkent Medical Academyfor the cooperation and support in our research.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
FUNDING
No funding sources to declare
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