Periodontitis is a chronic infectious inflammatory disease caused by microbes; however the presence of microbes is not enough for the cause of its complex nature of disease. Inflammation is the prime cause of periodontal disease. It commences with the aggregation of pathogenic microbes that induce the host to stimulate a cascade of inflammatory response reactions which in-turn leads to the destruction of the host tissues itself. There is a complex interplay of innate and adaptive immune responses which fights against the pathogens by direct interaction or by release of certain molecules including cytokines. Cytokines are cell signalling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. Cytokine biology reveals that there are some subsets of cytokines which are pro-inflammatory cytokines which stimulate the inflammatory responses and cause tissue destruction. A periodontist is expected to have a sound basis of the cytokine profile to understand the pathogenesis of periodontitis and also to discover the new treatment modality of anti-cytokine therapy.

2. CYTOKINES
Dr. Kritika Jangid
MDS- Periodontics

3. Cyto-cell.kine-movement
Cytokinesare lowmolecularweightsolublemediators(small
proteins)ofimmunitywhichare secretedbyactivated
immunocytesor somematrixcellsandpossesshighactivity
andvariousfunctions.

4.  Lymphokine: Made by activated
Lymphocytes especially TH cells, e.g.IL-2
 Monokine: Made by mononuclear
phagocytes, e.g.Mig/CXCL9
 Chemokine: Mediates chemotaxisbetween cells. e.g.IL-8, CXCL12
 Interleukin: interaction between leukocytes
IL-1, IL-8, IL-10, IL-13
 Named by activity: Tumor Necrosis Factor a (TNFa)
Colony Stimulation Facto(CSF)
Transforming Growth Factor b(TGFb)

5.  Low molecular weight proteins <30kd
 Active in pico-mole amounts
 Soluble mediators of immunity.
 Mechanism of leukocytes communication.
 Transient

6.  Produced by cells as part of normal cellular activity or the
result of environmentaltrigger
 Bind to receptors on cells
 Trigger signaltransduction pathways
 Initiatesynthesis of new proteins
 Only cells expressing receptors for specific cytokines can be
activated by them

7.  Autocrine
Affects the generating cell (self)
 Paracrine
Affects cells in the immediate vicinity
 Endocrine
Affects cells remote from the secreting cell

8.  PLEIOTROPISM
 REDUNDANCY
 SYNERGY
 ANTAGONISM
 CASCADE INDUCTION
 FORMACYTOKINE NETWORK.

9.  Abilityofonecytokinehavingdifferenteffectsondifferentcell.

10.  Thepropertyofmultiplecytokineshavingthesame or overlappingfunctional
effects.

11.  Thepropertyoftwoor morecytokineshavinggreater thanadditiveeffects.

12.  Theabilityofonecytokineinhibitingtheactionofanother.

13.  Actionofonecytokineona target cell
inducesthatcellto produce one or
more cytokines which induce other
target cellsto produce other
cytokines

14.  Onekindofcytokinescanbeproducedbydifferentcells.Onekindofcells
cansecretedifferentcytokines.
TH1
IL-2
IL-3,GM-
CSF,TNF-
IFN-γ,TNF-β
TH2
IL-4，6
IL-5

15.  Cytokinesinitiatetheiractionsby
bindingtospecificmembrane
receptorsontarget cells.

16. 1. Pro-inflammatorycytokines
2. CytokineswithPredominantimmuno-regulatoryfunctions
3. Cytokinesthatregulatelymphocytegrowth,activationanddifferentiation
4. Cytokinesthathelpinhematopoiesis
5. Chemokines

21. 1. Pro-inflammatorycytokines
2. CytokineswithPredominantimmuno-regulatoryfunctions
3. Cytokinesthatregulatelymphocytegrowth,activationanddifferentiation
4. Cytokinesthathelpinhematopoiesis
5. Chemokines

22.  IL-1
 TNF
 INF
 IL-6
 IL-8
 Macrophagemigrationinhibitionfactor(MIF)

23.  2molecularforms-IL-1α, IL-1β
 Encodedby2separategenes
 20%homology
 MainsourceofIL-1 arethecellsofmonocyte-macrophagelineage
 IL-1αtendstoremainassociatedtomembranes
 IL-1β -synthesisedasan inactiveprecursor,releasedfromthecellafter being
processedpost-transitionallybyacysteine-asparageneprotease

24.  IL-1β isexpressedbymonocytes,macrophagesanddendriticcells.
 Itsignalsthrough2receptors-IL-1R1 andIL-1RII bothofwhichare shared
withIL-1α
 Itisa multifunctionalmoleculetheeffectsrangingfrominflammation,
immunityandhemopoiesis
 IL-1 hasdiversactivitiesandrolesin
 immunity,
 inflammation,
 tissue breakdown and
 tissue homeostasis

25.  Involvedininflammatoryandimmuneresponses
 Bothautocrineandparacrineinducerofother cytokineslikeIL-1, IL-6, IL-8,
PDGF,ecosanoids,plateletactivatingfactorsandgranulocytemonocyte
colonystimulatingfactor
 TNFissecretedbymacrophages,monocytes,neutrophils,T-cells,NK cells
followingtheir stimulationbybacteriallipo-polysaccharides
 CellsexpressingCD4secreteTNF-αwhileCD8cellssecretelittleor noTNFα

26.  Directeffectonthepathogenesisofperiodontaldisease
 Up-regulatestheproductionofotherclassicpro-inflammatoryinnate
immunitycytokineslikeIL-1βandIL-6
 TNF- β is commonly known as lymphotoxin

27. 1. Metaboliceffects:AcutePhaseproteins-1-anti-trypsin,fibrinogen,CRP
2. Vasculareffects:Adherence.ExpressionofP-selectin,E-selectin
3. Endogenouspyrogen:DoesntcrossBBB, interactswitha groupofnucleiin
thehypothalamustocausefever

28.  Producedbyvarietyofcellslikemonocytes,fibroblasts,osteoblastsand
vascularendothelialcellsinresponsetoinflammatorychanges.
 Haspro-inflammatoryandhematopoieticactivity.
 Roleas a pro-inflammatorycytokineissimilartoIL-1 andTNF
 ActiononIL-6onB-cellsistheincreasedsecretionofIg-M
 InducesT-cellproliferation
 Pleiotropiccytokine

29.  Chemo-attractant for neutrophils
 Induced and secreted by monocytes, lymphocytes,
fibroblasts, epithelial and endothelial cells.
 Induces the adhesion of PMN to endothelial clls and
their trans-endothelial migration and release of
granulocyte enzymes from these cells
 Promotes angiogenesis
 Inhibits endothelial apoptosis

30.  Crucialroleintherecruitmentandactivationofmacrophagesas wellas in
helpingtokillthebacteria
 Alsoknownasglycosylation-inhibitingfactor(GIF)
 Innateimmuneresponses-TNF-α andTLR4expression,phagocytesand
intracellularkillingmechanisms
 Adaptiveimmuneresponses-Th1activationanddifferentiation

31.  IL-4
 IL-10
 IL-11
 IL-13
 IL-16
 TGF-β
 SolubleTNFreceptor
 SolubleIL-1 receptor

32. 1. Pro- inflammatory cytokines
2. Cytokines with Predominant
immuno-regulatory functions
3. Cytokins that regulate lymphocyte growth, activation
and differentiation
4. Cytokines that help in hematopoiesis
5. Chemokines

33.  Interferons
 IL-12
 IL-18

34.  Anti-viraleffects
 IFN-α- producedbyleucocytes
 IFN-β- producedbyfibroblasts
 IFN-γ- producedbyCD4+cellsandNK cells
 AlongwithIL-1, itinducesan increaseintheexpressionofICAM-1onthe
cytoplasmicmembrane ofendothelialcells,enhancingT-lymphocyte
adherencetothevascularendothelium.

37.  Regulationcytokine-initiationandregulationofcellularimmuneresponses
 Linksinnateandadaptiveimmuneresponses
 GeneratedfromT andB-lymphocytes,NK cellsandmacrophages.
 TheproductionisofIL-12 isinhibitedbyIL-4andIL-10.

39.  Recentlydiscoveredinterleukin
 Initiallynamedas interferonγ-inducingfactor
 Ithassimilar roleslikeIL-1andIL-12
 IL-18 isproducedandreleased byAPCsanditsmaintargetsare Th0/Th1
CD4+TcellsandNK cells

40. 1. Pro- inflammatory cytokines
2. Cytokines with Predominant immuno-regulatory
functions
3. Cytokines that regulate
lymphocyte growth, activation and
differentiation
4. Cytokines that help in hematopoiesis
5. Chemokines

41.  IL-2
 IL-4
 IL-5
 IL-12
 IL-15
 TGF-β

42.  Imp. for proliferation of T and B lymphocytes

43.  NecessaryforT celldevelopmentinthethymusforthe
maturationofa uniquesubsetofT cellsthatare termed as
regulatoryT-cells(T-regs)

44. • IL-4 isthemajorB-cellgrowthfactor
• VitalforimmunoglobulinclassswitchIgGtoIgEandinhibitsthesynthesisof
IgM andotherIgG subtypes
• IL-4 inducesexpressionofclassIImajor MHCmoleculesonB cells

45.  Suppresses the production of pro-inflammatory cytokines
 Suppresses the production of TNF-a, IL-1, IL-6 & IL-8
 Involved in the developmentof Th2 subset
 Involved in B-lymphocyte production
 Initiates growth of mast cells
 Stimulates synthesis of extracellularmatrix
 Cause the switching of antibody production to IgE and IgG

46.  RegulatesT cellandNK cellsactivationandproliferation
 ThenumberofCD8+memorycellsisshowntobecontrolledbya balance
betweenIL-15 andIL-12

47. 1. Pro- inflammatory cytokines
2. Cytokines with Predominant immuno-regulatory
functions
3. Cytokines that regulate lymphocyte growth,
activation and differentiation
4. Cytokines that help in
hematopoiesis
5. Chemokines

48.  Granulocyte- monocyte colony
stimulating factor
 IL-1
 IL-3 and Stem cell factor
 IL-6
 IL-7

49.  Majorcytokinestimulatinghaematopoiesis
 ReleasedbyactivatedT lymphocytes,stimulatinggranulocytesandmonocyte
cytotoxicactivityandexpressionofMHC-IImolecules
 Dendriticcellproliferationanddifferentiation
 B-cellproliferationanddifferentiation

50.  Actsas growthfactoronthebonemarrow
 Mobilisationofleukocyteswhichisreflectedintheperipheralbloodvessels
asleukocytosis
 Actsas growthfactorforearlybonemarrow progenitors
 ReleasedbyactivatedT-lymphocytes

51.  Imp. mediatoroftheosteoclastogenesisandbonelossininflammatory
conditionssuchasperiodontitis

52. 1. Pro- inflammatory cytokines
2. Cytokines with Predominant immuno-regulatory
functions
3. Cytokins that regulate lymphocyte growth, activation
and differentiation
4. Cytokines that help in hematopoiesis
5. Chemokines

53.  Cytokines that regulate the leukocyte movements

 2 groups depending on their structure- α and β
 α chemokine: Cys-X-Cys (CXC)
 β chemokine: CC

54. IL-8 (Neutrophil-Activatingfactor)
 ReleasedbyT-lymphocytesandmonocytesstimulatedwithTNFofIL-1
 Recruitsgranulocytestothearea ofinfection
 ChemotacticforT-lymphocytes

55. 4 major cytokines which act predominantly on mononuclear cells
 RANTES (Regulated onactivation, normal T-cell expressed andsecreted): Released
by T-cells, attracts T cells with memoryphenotype, NK cells, eosinophils and mast
cells
 MacrophageInflammatory proteins (MIP): Released by monocytes and
macrophages and attracts eosinophils, lymphocytes and NK cells
 MacrophageChemotactic Proteins (MCP): Produced by monocytes and
macrophages and related cells and attracts monocytes, eosinophils and NK cells
 Eotaxin: Induced byIL-4 that recruits eosinophils and Th2 CD41 T cells to the site of
allergic inflammation

58.  IL-1α,IL-1βandTNF-α-stimulateboneresorptionandinhibitbone
formation
 Chungetal has showedelevatedIL-1βexpressioninGCF atsitesofrecent
boneandattachmentlossinptswithperiodontitis
(Subgingivalmicrofloraandgingivalcrevicularfluidcytokinesinrefractory
periodontitis.JCP1995,Vol22)

59.  Studiesdoneonnon-humanprimatemodelsusingIL-1 antagonist(IL-1R)
haveshownsignificantreductionininflammation,connectivetissue
attachmentlossandboneresorptioninducedbyperiodontalpathogens
comparedtocontrols
Delima et al. Inflammation and tissue loss caused by periodontal pathogens is
reducedbyIL-1 antagonists. JInft Dis 2002

60.  Acceleratedprogressionofperiodontitisinrat ligaturemodelonapplication
ofrhTNF-α
Gillespie. Impact of cytokines and T-lymphocytes upon osteoblast differentiation
and function. Arthritis Res Ther2007
 TNF-αreceptor knockoutmicedevelopedsignificantlylessinflammationand
alveolarbonelossinresponsetoA.a
Garlet et al. The dual role of p55 TNF-α receptor in A.a induced experimental
periodontitis. Clin ExpImmunol 2007

61.  Studieshavedemonstratedthatconc.ofIL-4 inGCF decreasedfrom
periodontalhealthtodisease.
Bozkurt et al. Anti-inflammatory cytokines in GCF in pts with periodontitis and RA:
a preliminary report. Cytokine 2006
Pradeepetal. GCF levels of monocyte chemoattractant protein 1 in periodontal
health and disease. Archives of Oral Biol 2009

62.  IL-6 higherininflammedgingivalfluid
Bartold. IL-6 in human gingival fibroblasts. JPR 1991
 GeneticallydeletedIL-6- decreasedboneloss
Bakret al. T-cells and the pro-inflammatory cytokines gammainterferon and IL-6
contribute to alveolar bone loss in mice. Infect Immunol 1999

63.  IL-8 conc.higherinpockets<3mmandlessin>6mm
McGee etal.The relationship between concentrations of proinflammatory
cytokines within gingiva and the adjacent sulcular depth. JOP 1998

64. IL-33-anti-inflammatoryandreparative responses
 TNF-αinducedIL-33 maylinkinflammationdirectlytotheIL-33-dependent
stimulationofTh2cytokineproducingcellswhichresultsinanti-
inflammatoryandreparativeresponses
Beklen etal. IL-1 superfamily memberIL-33 in periodontaln diseases. Biotech
Histochem April-2014

65.  Aggressive: IL-17
 Control: IL-11
IL-17 and IL-11 GCF levels in Aggressive and Chronic Periodontitis patients.
Shakeretal. Mediators of inflammation 2012

66.  Downregulationof expressionofosteoblastandosteocytemarkers in
periodontaltissuesassociatedwiththespontaneousalveolarbonelossofIL-
10knockoutmice
Claudino etal. European Journal ofOral Sciences 2010

67.  IL-18isincreasedinchronicperiodontitisafter bacterialinfectionvia T-cell
mediatedpathway
Yoshinaka et al. IncreasedIL-18 in gingival tissues evokes chronic periodontitis
after bacterial infection. The Tohoku Journal of Experimental Medicine 2014

68.  IL-29hasantiviralpropertiesandsmokingcausesimbalanceintheGCF ofIL-
29
Shivaprasad et al. Influence of smoking onIL-29 (IF-γ1) levels in GCF of Chronic
Periodontitis pts. Journal of dental Sciences.2014

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