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Overview and historical significance of inflammation DrLindaMayerandProfRashidBhikha November2013 GeneraloverviewofInflammation Thephenomenonofinflammationhasbecomingmoreimportantoverthelastfewyears,as werealizeitsextensiveinvolvementinmoreandmoredisorders.Bronchialasthmawas identifiedasaninflammatorydisorderabout20yearsago,followedbyvariousother allergies.Sincethenmanyothers,suchasdiabetesI,Alzheimer’s,variouscancers,some heartdiseasesandevenageinghavebeenidentifiedaseitheracuteorchronicinflammatory disorders(Glynn,2013). Tibbisverymuchcentraltothis,asthenormalinflammatoryresponse,Physisand inflammationarecloselymeshedwithlifestyle,especiallydiet.Oneofthemostprevalent underlyingbeliefsabouthealthintheWesternworldisthatillnessisamistake,andthat symptomsofadiseasemustbeeradicatedonordertorestorehealth.Whatisdefined negativelyas‘pathology’bywesternmedicineisoftenthebody’sattempttoreachfor health. Mistrustingthebody’sabilitytoself-heal,resultsinadeepandwidespreadfearofillness.In ordertochangetheparadigmofadisease-basedapproachtoaperson-centredone,a consciousshiftisneeded,fromfearingsymptomstounderstandingandembracingthe innatehealingabilityofPhysistorestoreinternalbalance. Thesourceoftheinflammationneedstobefoundbyidentifyingthetriggerfactorswhich causetheinflammation,whichincludesphysical,environmental,emotional,chemical,and mostimportantnutritionalfactors. Understandingtheimportantroleandstagesofinflammationintheprocessofhealingis fundamentaltopreventchronicanddebilitatingdiseasesformoccurring.Theprevailing signsandsymptomsofanacuteinflammatoryresponsearebothwarningandprotective mechanismsofthebody,whichenablestheimmunesystemtorespondaccordingly.Any attemptstoimpedethisnaturalprocesswillinterferewiththeinnatehealingabilityof Physis. Inflammationisanimportantmanifestationofthenaturalbody’sresponsetoinjury,which isanecessaryrequisitetohealing.Variousapproachestomanaginginflammationvary accordingtotheconventionalallopathicorothercomplimentaryhealthdisciplines. Interferingwiththenaturalinflammatoryresponsecanresultinpathologyandchronic inflammation. Theunderlyingcausesformanydiseaseshavetheiroriginsinpoorlifestylechoices,which mayresultinchronicsystemicinflammation,suchasobesity,diabetes,highbloodpressure, andgout.Hiddeninflammationisnotaseasilydetectedasanacuteinflammatoryresponse, anditisalothardertocontrolandmanage,especiallybecauseoftheincreasingpropensity oflifestyle-induceddiseases.Chronicsystemicinflammationisanunderlyingcauseofmany seeminglyunrelated,age-relateddiseases.However,theyareallrelatedbyanimbalanceof theinternalenvironmentinthebody. Theconventionalapproachtoinflammationfacilitateshealingbyintroducingtreatment methodswhichcontrolsandeveninhibitstheinflammatoryprocess,mainlywith medication.TheTibb’sapproachtoinflammationistomaintainthehumanbodyinastate ofbalance,harmonyandvigour,byallowingPhysistogothroughthevariousstagesofthe inflammatorystagesandprocessinordertofacilitatehealing.Thephysical,mental, emotionalandspiritualforcesofhumanlifeneedtoberespected,astheyareall contributoryfactorstotheoutcomesofhealthanddisease. TheTemperamentofanindividualdeterminesthespecificeliminativetherapywhichwillbe adoptedtomaintainandrestorehealth,andinthepreventionandmanagementof inflammationandanyotherdisease.Tibbalsounderstandthatthelifestylefactorsplaya pivotalroleinthisprocess.Thisincludesenvironmentalairandbreathing,foodanddrink, movementandrest,sleepandwakefulness,emotionsandeliminationandretention. InTibbtherelationshipofheat,moistness,coldnessanddrynesshasadirectbearingonthe healthstatusofanindividual.Heatisgenerallymorefavourablethancoldformaintaining theproperbalanceandgeneralhealthofthebody.Healthwillonlybemaintainedaslong astheoverallqualityofthehumoursisinharmonywiththeoverallqualityofthe individual’stemperament. DefinitionsofInflammation Inflammationisassociatedwithheatviathesymbolofaflame.Thewordinflammation comesfromtheLatin"inflammo",meaning"Isetalight,Iignite"or“inflammare(toset alight).TheancientGreeksreferredtoinflammationasa“hotthing.”TheGreekword, “phlegmon"wasusedtodescribeinternalinflammatorylesions(Nordqvist,2012). Thedefinitionofinflammationdependsonwhetheroneviewsthisfromaclinical,cellularor molecularperspective,butisclearthatitembracesagreatvarietyofbiologicalprocesses, whichismodulatedbymanyfactorsinthecell’senvironment(Scottetal,2004).The definitionofinflammationhaschangeddramaticallysinceitwasfirstusedbyCelsusnearly 2000yearsago. Defininginflammationaccordingtoclinicalsignsandsymptomshasmajorlimitations,asin mostcasesthecellularprocessesandsignalsthatunderliethecardinalsignsoccurata subclinicallevelanddonotgiverisetoanyheat,redness,swelling,orpain.Forexample, theinflammationofdelayedonsetmuscularsorenessmaycausetendernessonpalpationor milddiscomfort,butnorednessorswelling.Thedefinitionalsodependsontheparticular perspectiveoneisviewinginflammation-whetheritbeclinical,cellular,ormolecular(Scott etal,2004). Inflammationisalocalisedprotectiveresponseelicitedbyinjuryofdestructionoftissues, whichservestodestroy,dilute,orwalloffboththeinjuriousagentandtheinjuredtissue (Saunders,2007).Itisanormalresponsetodisturbedhomeostasiscausedbyinfection, injury,andtrauma.Thehostrespondswithacomplexseriesofimmunereactionsto neutralizeinvadingpathogens,repairinjuredtissues,andpromotewoundhealing(Pavlov, etal,2003).Itisaphysiological,protectiveresponsetoinjuryortissuedestruction,whichis self-limiting;however,pathologymaydevelopifthenaturalhealingresponseofPhysisis tamperedwith. Inflammationisacomplexprocessinvolvingthecirculatorysystemandblood-borncells.It isanaturalbodyresponsetoaninjury,beitofphysical,chemicalorinfectiousorigin,andit isanecessaryprocessforhealing(MerckAnimalHealth,2013). Thecommonsorethroat,rashesorasprainedankleareprotectiveresponsesofthebodyto inflammation,whichcommunicatesdistressinthebody.Theproblemariseswhen: • • Thereisanoverreactionoftheimmuneresponse,inconditionssuchasallergies, asthma,autoimmunediseasesorrheumatoidarthritis. Thereisnoovertorvisiblesignofinflammation,whichisattherootofallchronic diseases,suchindiabetes,heartdisease,cancer,dementiaanddepression.This inevitablyresultsinachronic,smoulderinginflammationthatslowlyinterfereswith optimalfunctioningbydestroyingtheorgans,leadingtorapidageing(Hyman, 2012). Thenaturalanti-inflammatoryresponsethatensuesafteracuteinflammationtendsto reversetissuehomeostasistowardsnormality,andshouldthereforeberegardedasatrue defensivereactionoftheaffectedtissue.Inflammationisnowrecognizedasatypeof nonspecificimmuneresponse.”“Inflammationisthebasicprocesswherebytissuesofthe bodyrespondtoinjury.”Allsignshavebeenregardedassecondarytooneprimary pathophysiologicalevent–enhancementofvascularpermeabilityasadirectconsequence oftissueinjury(Stankov,2012). IncidenceandPrevalenceofInflammatoryDiseases Immune-mediatedinflammatorydiseasesareagroupofcommonandhighlydisabling chronicconditionsthatshareinflammatorypathways.ItsestimatedprevalenceinWestern societyis5%-7%(Gabalawyetal,2010).Inflammatorydisordersareincreasingduetopoor lifestylechoices,especiallydiet,andincludeallergy-relateddisorders,suchasasthma, diabetes,heartdiseases,certaincancers,Alzheimer’sdiseaseandevenageing,amongsta hostofotherconditions. AccordingtotheMarshallProtocolKnowledgeBaseforAutoimmunityResearchFoundation, in2004133millionpeople(halfofallAmericans)livewithchronicconditions.Thisaccounts for83%ofthehealthcarespending,andthosewith5ormorechronicconditionshavean averageof15physicianvisitsperyear,withmorethan50prescriptionsperyear(Wood, 2004).TheJournaloftheAmericanMedicalAssociationpublishedapaperin2010, highlightingtherateatwhichchronichealthconditionsamongchildrenintheUnitedStates increasedfrom12,8%in1994to26,6%in2006(VanCleaveetal,2010). AccordingtotheInternationalJournalofEndocrinologytheglobalemergenceofobesity increasestheriskofdevelopingchronicmetabolicdisorders,whichisassociatedwith chronicsystemicinflammation.From2005-2006ithasshownthat33.3%ofmenand35.3% ofwomenwereobese(Hernandezetal,2013). TheincidenceandprevalenceofInflammatoryboweldiseasereincreasingwithtimeandin differentregionsaroundtheworld(Molodeckyetal,2012).Inoneofthelargeststudies, baseduponninemillionhealthinsuranceclaims,theprevalenceofulcerativecolitisin adultsintheUnitedSateswas238per100,000population,andtheprevalenceofCrohn's diseasewas201per100,000population. Rheumatoidarthritis(RA)andosteoarthritis(OAO)arethetwomostcommonrheumatic diseases,accountingforalargepercentageofdisabilityworldwide,creatinghugehealth, socialandeconomicburdens(Sanga,2000). Goutisthemostprevalentformofinflammatoryarthritis. TheAmericanCollegeof RheumatologyhasshownthattheprevalenceofgoutintheU.S.hasrisenoverthelast twentyyearswhichcurrentlyaffects8.3million(4%)Americans.Thismaybeassociated withahigherincreaseinobesityandhypertension(Wiley-Blackwell,2011) AHistoricaloverviewofinflammation InfectionscausedbyGroupAStreptococcus(GAS)isahumanpathogenwhichisresponsible formanydiseases,rangingfromstreptococcalpharyngitistoimpetigo.Infectionswhich werecausedbyGAShavebeendocumentedasfarbackas6500BC.Inthelate17thcentury, ThomasSydenhamclinicallydistinguishedscarletfeverfrommeasles(Leday,2006). RecordsofholisticmedicinegobacktotheEgyptiangodofmedicine,Imhotep,wholivedin 2980BC.TheoriginsofEgyptianmedicinelieinreligionandspirituality,anditwasbelieved thatthegodsintervenedinmattersofhealthanddisease.Atthattimeitwasrecognised thatbloodwasthenutritiveandregulatorysubstanceandtheheartwasthecentreofthe circulatorysystem.Itwaswidelyrecognisedthatrespiratorypatternsinfluencedblood circulation. Earlyconceptsaboutinflammationwerelargelyderivedfromintuitionratherthancareful scientificinvestigation,butwhichprovidedtheframeworkforcriticalexperimentationinthe latercenturies.ThehistoryofinflammationdatesbacktotheancientEgyptianandGreek cultures.In1650theancientEgyptiansrecordedtheearliesttranscriptsonpapyrus (Nordqvist,2012). Hippocrates(460-370BC)introducedtheterm,‘woundputrefaction’(‘sipsi’–makerotten), meaningenzymedecomposition,especiallybyproteins,withtheproductionoffoul-smelling compounds(Saunders,2007). Galen(130-201AD)viewedinflammation,particularlypus,aspartofthebeneficialreactive responsetoinjury(Phlogosis),ratherthanasuperimposedpathology(Scottetal,2004; Silva,1978). Avicenna(979-1037BC)observedthatthecoincidenceofbloodputrefaction,namely, septicaemiawasusuallyaccompaniedbyfever. Thedoctrineofthefourcardinalsignsofinflammation,namely:redness(rubor),swelling (tumor),heat(calor)andpain(dolor),wasoriginallytermedbyAulusCorneliusCelsusinthe 1stcenturyAD(Rather,2012). TheFrenchchemist,LouisPasteur(1822-1895)discoveredthattinysinglecellorganisms causedputrefaction.Hecalledthembacteriaormicrobesandcorrectlydeductedthatthese microbescouldbecausingdisease(GermanSepsisSociety,2013).LouisPasteurlinkedthe decayoforganicsubstancestothepresenceofbacteriaandmicroorganisms,whichwere killedbyheating. RudolphVirchow(1821-1902)wasaGermanphysician,anthropologist,politicianand founderofthefieldofcellularpathology.Heviewedinflammationasinherently pathological.Hestressedthatmostofthediseasesofmankindcouldbeunderstoodin termsofthedysfunctionofcells(Edwards(2013).Histheoryofcellularpathologybecamea basisfortheunderstandingandfightagainstpathologicalprocessesinlivingorganisms. Virchowdescribedtheinflammatoryprocessashavingbeenderivedfromtheincreased activity(nutritiveirritability)ofthecelltofindtheappropriatesourceoffoodinthe surroundingtissues.Heconcludedthat‘theinflammatoryreactionisaconsequenceofan excessiveintakebyinterstitialcellsoffoodfromtheliquidpartoftheblood,filtering throughthevesselwall’,whichwouldresultinhypertrophy,ordegenerationofthecells, whichwouldmultiplytoformaninflammatorytumour(Silva,1978). Virchowcreatedthenewparadigmofcellularpathologywhenhecriticallyanalysedthe meaningofthefourkeysymptomsofinflammationandproposedthatinflammation constitutesvariousinflammatoryprocesses.Heisalsosaidtobeaccreditedtohave introducedthefifthcardinalsign–“functionlaesa”,orlossoffunction,wherebyheviewed inflammationasinherentlypathological.Hehighlightedtheimportanceofthe inflammatorystimulus(Heidlandetal,2006).IncontrastwithGalen,Virchowviewed inflammationasinherentlypathological(Scottetal,2004). ElieMetchnikoff(1845-1916)isconsideredtobethefatherofnaturalimmunity,and, togetherwithPaulEhrlich,theywerethepioneersofcellularandhumoralimmunology. Metchnikoffisrecognisedforthebiologicalsignificanceofleukocyterecruitmentand phagocytosisofmicrobesinhostdefenceagainstinfection,inflammationandimmunity (Gordon,2008).Heobservedthatneutrophilgranulocytes(microphages)wereremoved fromtheinflamedsitebybeingingestedbymacrophageswhilestillintact(Savill,1997). SirJosephLister(1827-1912),theFatherofmodernsurgery,introducedtheantiseptic methodbydisinfectingwithcarbolicacid,whichwasalsousedduringthisperiodasan effectivedisinfectantinsewers.Healsosprayedtheairwithcarbolicacidtokillairborne germs.Listerisquotedtohavesaid:‘Anyonetryingtowirethebrokenpiecestogether withouttheantiseptictechniquewouldbefacedwithaninfectedkneeandhospital gangrene’(Lamont,1992).Healsointroducedsterilisedcatgutforinternalsutures. FriedrichDanielvonRecklinghausen(1833-1910)characterizedthepuscellsinacute inflammation,andheshowedthatpuscellscouldmigratefromtheplacesoftheiroriginin theinterstitiumtoothertissuesandepithelialcells.Healsocontributedtotheconceptof phagocytosis(Heidlandetal,2009). JuliusFriedrichCohnheim(1839-1884)observedthedilatationofthearteriesandveins, adhesionofcolourlesscellstotheendothelialcells,andthesubsequenttransmigrationfrom thecapillariesandvenulesintotheinterstitialspace(Heidlandetal,2009).Cohnheimwas Virchow’spupil,producedmanyobservationswhicharetheantecedentsofmodern conceptsininflammation.Heshowedthattheoriginsofpuscellsarefromthebloodand notfromlocaltissueelements,asVirchowbelieved(Prichard,1961). IgnazSemmelweis(1818-1865)deductedthatchildbedfeverwascausedby"decomposed animalmatterthatenteredthebloodsystem".Heintroducedhandwashingwitha chlorinatedlimesolutionbeforeeverygynaecologicalexamination,butthehygienic measureswerenotacceptedatthattime(GermanSepsisSociety).Semmelweisobserved thesignificanteffectofhygienicmeasuresondecreasingthemortalityofwomenduring childbirth(Rittirschetal,2008;Kubendiran,2011). HugoSchottmüller(1867-1936)explained:"Sepsisispresentifafocushasdevelopedfrom whichpathogenicbacteria,constantlyorperiodically,invadethebloodstreaminsuchaway thatthiscausessubjectiveandobjectivesymptoms."Healsomaintainedthat:"Atherapy shouldnotbedirectedagainstbacteriainthebloodbutagainstthereleasedbacterial toxins’(GermanSepsisSociety). RogerC.Bone(1941-1997)definedsepsisas“aninvasionofmicroorganismsand/ortheir toxinsintothebloodstream,alongwiththeorganism'sreactionagainstthisinvasion."He influencedthedevelopmentofnewtherapeuticstrategiesbyhavingelucidatedthevarious stagesorphysiologicalterationsthatoccurinthesepticpatient(Balk,2011). AboutacenturyagoPaulEhrlichproposed“horrorautotoxicus”asimmunereactivity againstself,whichisnowcalledautoimmunity.In1957Burnetandothersdemonstrated thepresenceofautoantibodiesandprovidedatheoreticalbasisforautoreactivity(Amagai &Matsushima,2010). Advancesinmicroscopyandcellbiologyinthe19thcenturygaverisetocellbased definitionsofinflammation.Researchersbegantoquestionwhetherinflammationwasa singleprocess.Inthemiddleofthe19thcenturyscientificmethodswerevigorouslyapplied toascertainthecausesofmanyinfectionsbygermsandviruses.Bytheendofthe19th centuryitwasacknowledgedthatchangingcellpopulationsarisingfromboththebloodand localproliferationwereakeyfeatureofmanymodelsofinflammation(Scottetal,2004). Summary Thepioneersofindividualswhorecognisedandunderstoodtheprocessesandmechanisms ofinflammationhaveledtomanyadvancesinthefieldofinflammatorydiseases.However, theglobalincreaseofdisordersassociatedwithpooreatinghabits,smoking,lackofexercise andsleep,arejustafewexamplesofincreasingincidencesandprevalenceofchronic inflammatorydiseases. Theroleoflifestylefactorsplaysapivotalroleintheoverallhealthandwellbeingofan individual.Thisincludessensiblechoicesforlivinglifeashealthyaspossiblewithinthe parametersofeachperson’sidealTemperament,whichconsiders:environmentalairand breathing,foodanddrink,movementandrest,sleepandwakefulness,emotionsand eliminationandretention.Otherinterventionstoliveahealthyanti-inflammatorylifestyle, ortoassistthebodytorestoreitbacktohealth,includeTibbherbalmedication,herbal stimulants,vitamins,aswellastissuesalts. Inordertochangetheparadigmofadisease-basedapproachtoaperson-centredone,a consciousshiftfromfearingsymptomstounderstandingtheinnatehealingabilityofPhysis torestoreinternalbalanceisneeded.TheaimistoassistPhysisinthehealingprocessand nottostoporinterruptitsprogress. References Nordqvist,C.(2012).WhatIsInflammation?WhatCausesInflammation.[Online]. Availablehttp://www.medicalnewstoday.com/articles/248423.php Scott,A.,Khan,K.M.,Cook,J.L.,Duronio,V.(2004).Whatis“inflammation”?Areweready tomovebeyondCelsus?AnInternationalpeer-reviewedjournalofsportandexercise medicine.BrJSportsMed2004;38:248-249doi:10.1136/bjsm.2003.011221.[Online]. Availablehttp://bjsm.bmj.com/content/38/3/248.full Saunders.(2007).Dorland’sIllustratedMedicalDictionary.USA:Elsevier. MerckAnimalHealth(2013).PyrexiaandInflammation.[Online].Available http://www.banamine.com/research/pyrexiainflammation.asp Hyman,M.(2012).UltraWellnessLesson2:Inflammation&ImmuneBalance.[Online]. Availablehttp://drhyman.com/blog/2010/04/28/ultrawellness-lesson-2-inflammationimmune-balance/ Stankov,S.V.(2012).DefinitionofInflammation,CausesofInflammationandPossibleAntiinflammatoryStrategies.TheOpenInflammationJournal,2012,5,1-9.[Online].Available http://benthamscience.com/open/toinfj/articles/V005/1TOINFJ.pdf Gabalawy,H.;Guenther,L.C.;Bernstein,C.N.(2010).Epidemiologyofimmune-mediated inflammatorydiseases:incidence,prevalence,naturalhistory,andcomorbidities.J RheumatolSuppl.2010May;85:2-10.doi:10.3899/jrheum.091461.[Online].Available http://www.ncbi.nlm.nih.gov/pubmed/20436161 Glynn,J.(2013).PersonalnotesfromanemailtoLindaMayer. Wood,R.(2004).CurrentprevalenceofchronicdiseasesintheUnitedStates.[Online]. Availablehttp://mpkb.org/home/pathogenesis/epidemiology VanCleave,J.;Gortmaker,S.L.;Perrin,J.M.(2010).Dynamicsofobesityandchronichealth conditionsamongchildrenandyouth.JAMA.2010;303:623-30.[Online].Available http://www.ncbi.nlm.nih.gov/pubmed/20159870 Hernandez,H.R.;Simental-Mendia,L.;Rodriguez-Ramirez,G.;Reyes-Romero,M. (2013).ObesityandInflammation:Epidemiology,RiskFactors,andMarkersofInflammation. [Online].Availablehttp://www.hindawi.com/journals/ije/2013/678159/ Molodecky,N.A.;Soon,I.S.;Rabi,D.M.;Ghali.W.A.;FerrisM.;Chernoff.G.;Benchimol, E.I.;Panaccione,R.;Ghosh,S.;Barkema,H.W.;Kaplan,G.G.Increasingincidenceand prevalenceoftheinflammatoryboweldiseaseswithtime,basedonsystematicreview. Gastroenterology.2012Jan;142(1):46-54.e42;quize30.doi:10.1053/j.gastro.2011.10.001. Epub2011Oct14.Availablehttp://www.ncbi.nlm.nih.gov/pubmed/22001864 Sanga,O.(2000).EpidemiologyofRheumaticDiseases.Rheumatology2000;39(suppl.2):312.[Online].Available http://rheumatology.oxfordjournals.org/content/39/suppl_2/3.full.pdf Wiley-Blackwell.(2011).GoutPrevalenceSwellsinU.S.OverLastTwoDecades;Increasein ObesityandHypertensionAreLikelyContributors.[Online].Available http://www.sciencedaily.com/releases/2011/07/110728082551.htm Leday,T.(2006).UseofanAnimalModelofGroupAStreptococcalInfectiontoIdentify FactorsImportantforVirulence.PDFversion:KevinS.McIverMelanieH.CobbEricJ.Hansen -Repositories.[Online].Nowebpagereference. Rather,L.J.(1971).Disturbanceoffunction:Thelegendaryfifthcardinalsignof inflammation,addedbyGalentothefourcardinalsignsofCelsus.DepartmentofPathology StanfordUniversitySchoolofMedicine.[Online].Available http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1749862/pdf/bullnyacadmed002040099.pdf Noauthor.SepsisHistory.GermanSepsisSociety.[Online].Availablehttp://sepsisgesellschaft.de/DSG/Englisch/Disease+pattern+of+Sepsis/Sepsis+History?iid=2 Edwards,S.A.(2013).RudolpgVirchow,thefatherofcellularpathology.[Online].Available http://membercentral.aaas.org/blogs/scientia/rudolph-virchow-father-cellular-pathology Silva,M.R.E.(1978).ABriefSurveyoftheHistoryofInflammation.Agentsandactionsvol.8/ 1-2,Basel.[Online].Availablehttp://link.springer.com/article/10.1007%2FBF01972401#page2 Heidland,A.,Klassen,A.,Rutkowski,P,andBahnerU.(2006).ThecontributionofRudolf Virchowtotheconceptofinflammation:whatisstillofimportance?J.Nephrol.May-Jun;19 Suppl10:S102-9.[Online].Availablehttp://www.ncbi.nlm.nih.gov/pubmed/16874721\ Gordon,S.(2008).ElieMetchnikoff:fatherofnaturalimmunity.EurJImmunol.2008Dec; 38(12):3257-64.[Online].Availablehttp://www.ncbi.nlm.nih.gov/pubmed/19039772 Savill,J.(1997).Apoptosisinresolutionofinflammation.[Online].Available http://www.jleukbio.org/content/61/4/375.full.pdf Lamont,A.(1992).JosephLister:FatherofModernsurgery.[Online].Available http://www.answersingenesis.org/articles/cm/v14/n2/joseph-lister#fnList_1_5 Heidland,A.,Klassen,A.,SebekovaK,BahnerU.(2009).Beginningofmodernconceptof inflammation:theworkofFriedrichDanielvonRecklinghausenandJuliusFriedrich Cohnheim.JNephrol.2009Nov-Dec;22Suppl14:71-9.[Online].Available http://www.ncbi.nlm.nih.gov/pubmed/20013736 Prichard,R.(1961).SelectedItemsfromtheHistoryofPathology.AmJPathol.1979 November;97(2):314.[Online].Available http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042458/pdf/amjpathol00237-0113.pdf Rittirsch,D.;Flierl,M.;Ward,P.(2008).Harmfulmechanismsinsepsis.NatRev Immunol.2008October;8(10):776–787.[Online].Available http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786961/ Balk,R.(2011).RogerC.Bone,MDandtheevolvingparadigmsofsepsis.Contrib Microbiol.2011;17:1-11.[Online].Available http://www.ncbi.nlm.nih.gov/pubmed/21659744 Amagai,M.;Matsushima,K.(2010)Overviewonautoimmunityandautoinflammation. [Online].Availablehttp://www.jsir.gr.jp/journal/Vol31No1/pdf/06_S1_50.pdf