Ibanjwe nguGqr. Wen-Chang Chang, usihlalo webhodi yabalawuli yeYunivesithi yezoNyango yaseTaipei, kunye noGqr. Yun Yen, uprofesa ongusihlalo kwiYunivesithi yezoNyango yaseTaipei, le seshoni ikhethekileyo ibonise iintetho ezinikezelwa ngabaphumeleleyo abathathu kwi-2020 Tang Prize kwi-Biopharmaceutical Science. , uGqr. UCharles Dinarello, uMarc Feldmann, kunye noTadamitsu Kishimoto, banikezela ngolwazi oluxabisekileyo ngendima edlalwa ziicytokines ekudumbeni nakwisifo se-COVID-19 kunye nonyango olunokwenzeka.
Intetho yokuqala kaGqr Dinarello, enesihloko esithi "Interleukin-1: I-Prime Mediator of Systemic and Local Inflammation," yaqala ngokuhlanjululwa kwe-leukocytic pryogen kwiiseli zegazi ezimhlophe zomntu ngo-1971. Kwamthatha iminyaka emithandathu ukuchonga ifiva ezimbini- ukuvelisa iimolekyuli, kamva ebizwa ngokuba yi-IL-1α kunye ne-IL-1β. Ngowe-1977, iziphumo zophando zapapashwa kwiProceedings of the National Academy of Sciences, yaye kuGqr. Dinarello, “leyo yayilinyathelo elibalulekileyo kwimbali ye<em>cytokine biology,” kuba abantu abaninzi kwinkalo yenzululwazi yobomi bakhuthazwa ukuba funda ifuthe lenkqubo yomzimba yokuzikhusela kwi-physiology yabantu. Ngenxa yoko, ibhayoloji yecytokine yanda ngokukhawuleza. Kwakhona wathetha malunga nendlela emva kovavanyo lokuqala ebantwini, "imbali ye-cytokines esetyenziswa njengonyango yatshintsha kakhulu," kwaye ingqwalasela yatshintshelwa "ekuthinteleni ii-cytokines, ezifana ne-IL-1, njenge-TNF, njenge-IL- 6.” Ukunceda abaphulaphuli baqonde inethiwekhi eyinkimbinkimbi eyenziwe ngamamolekyuli ane-pro-inflammatory yentsapho ye-IL-1, uDkt Dinarello wachaza ngokubanzi ukutshintshwa kwesignali ye-IL-1 amalungu omndeni, iimpawu zabo ezichasene ne-anti-inflammatory, kunye neempawu ze-IL-1. izifo ezahlukeneyo ezivuthayo, ukwenzela ukuba kube lula ukuba abaphulaphuli bafumane ukuqonda okufanelekileyo kwisiqingatha sesibini sentetho egxile "kwisicelo seklinikhi ye-Il-1 blockade." I-IL-1 overproduction, njengoko uDkt Dinarello wathi, yimbangela eqhelekileyo yezifo ezininzi. I-IL-1Ra, ngakolunye uhlangothi, inokuvimbela i-Il-1αandβ, kwaye ivimbele ukubonakaliswa kwe-IL-1R. I-Anakinra, i-IL-2Ra yomntu ephinda iveliswa. Isetyenziselwa ukunyanga i-rheumatoid arthritis kwaye inokuthintela ukuphazamiseka kwe-glycemic kuhlobo lwe-1 yeswekile. Ngaphezu koko, i-canakinumab, i-anti-IL-1βmonoclonal antibody ephuhliswe ngempumelelo nguNovartis, ivunyiwe kwizifo ezahlukahlukeneyo, ukusuka kwizifo ezinqabileyo zefa, izifo ze-rheumatic, izifo ezizimele kunye nezifo ezivuthayo, kwizifo zentliziyo. Ezona ndaba zimnandi kakhulu ezibandakanya i-canakinumab lulingo lwezonyango, i-CANTOS, ebonakalise ngokungalindelekanga ukuba i-canakinumab inendima ebalulekileyo ekunyangeni umhlaza. Ngoko ke, uGqr. Dinarello ukholelwa ukuba ukuvimba i-IL-XNUMX kunokungenisa ukusa kwonyango olutsha lomhlaza.
Isithethi sesibini, uGqr. Feldmann, wabelane ngeembono zakhe "Ukuguqulela i-Molecular Insights kwi-Autoimmunity ibe yi-Effective Therapy." Ugxininiso lwesiqingatha sokuqala sentetho yakhe yindlela afumanisa ngayo ukuba i-anti-TNF inokusebenza kakuhle ekunyangeni i-rheumatoid arthritis. Ukulawula iidosi eziphezulu okanye eziphantsi kweli chiza kunokuthintela i-TNF ngelixa kunciphisa ngokukhawuleza imveliso yabanye abalamli abavuthayo. Kwiimvavanyo zabo zangaphambili, uGqr. Feldmann kunye neqela lakhe babonise ukuba malunga ne-50% yabantu abane-rheumatoid arthritis baphendule kunyango oludibeneyo usebenzisa i-anti-TNF kunye neyeza lomhlaza i-methotrexate. Oko kwamkhokelela ekubeni akholelwe ukuba “inde indlela ekufuneka siyihambile ngaphambi kokuba sonke isigulana siphiliswe.” Ngexesha lesiqingatha sesibini sentetho, uGqr. Feldmann wasichazela ukuba "i-TNF ngumcamngca ongaqhelekanga kakhulu, kuba ineethagethi ezimbini ezahlukeneyo: i-TNF receptor-1 (TNFR1), eqhuba ukuvutha, kunye ne-TNF receptor 2, eyenza kakhulu. ngokuchaseneyo. Ke ukuba uvimba yonke i-TNF, uvimba i-receptors. Uyakuthintela ukudumba, kodwa ukwathintela iinzame zomzimba zokuthomalalisa ukudumba.” Ngoko ke, yena kunye noogxa bakhe "kwinkqubo yokuvelisa izixhobo" kwaye sele ivimbile i-TNFR1 ngaphandle kokutshintsha umsebenzi weeseli ze-T ezilawulayo. Ukongezelela, uDkt Feldmann ukhankanye amandla okuchasana ne-TNF yokujongana neemfuno ezininzi zonyango ezingafezekanga, ezifana nokunyanga i-fibrosis yesandla ngokujova i-anti-TNF entendeni. Nangona kunjalo, wachaza izinto ezingalunganga ezimbini ezicacileyo ze-anti-TNF awaqala ukuyiphuhlisa: yayingabizi kakhulu kwaye "yayisiyobisi esitofwayo." Ngaloo ndlela, ukwenza “iziyobisi ezingabizi mali ininzi zinokuhanjiswa ngomlomo” bekuya kuzisa iingenelo ezingakumbi kwibutho labantu. Kuyo yonke le ntetho, uGqr. Feldmann waqhubeka ekhulisa abantu abaninzi awayekunye nabo okanye asebenzisana nabo kwiiprojekthi ezahlukeneyo kunye novavanyo, njengoko wayezama ukubethelela umyalezo wokuba oko akufundileyo kula mava “yayiyindlela yokusebenza ngokufanelekileyo nabanye” ukuqinisekisa impumelelo eqhubekayo kuphando lwabo. Ibe luphawu lomsebenzi wakhe wokufumana “abantu abanetalente asebenza nabo,” kunye, “kunye nabo,” ukuze baphumeze okungaphezulu “kunokuba besinodwa.”
Enikezela ngentetho yesithathu ngesihloko esithi "Interleukin-6: Ukusuka kwiArthritis ukuya kwi-CAR-T kunye ne-COVID-19," uGqr. Kishimoto utsalele ingqalelo yabaphulaphuli kwindlela i-IL-6 yafunyanwa ngayo, kutheni i-IL-6 iyimolekyuli yepleiotropic, kwaye kutheni. I-IL-6 "inoxanduva lokuvelisa zombini i-antibody kunye nokungeniswa kokudumba." Kwakhona wakhanyisa iziphumo ze-IL-6 kwizifo ezizimele kunye nendlela i-IL-6 inokubangela ngayo iziphepho ze-cytokine. Ekuqaleni kwentetho yakhe, uDkt. Kistimoto wacacisa ukuba ukuveliswa kwe-IL-6 kuye kwafumanisa ukuba kudibene nezifo ezininzi, ezifana ne-cardiac myxoma, isifo se-Castleman, isifo se-rheumatoid arthritis, kunye ne-systemic start of juvenile idiopathic arthritis (JIA). Ukujongana neempendulo ezivuthayo ezibangelwa yi-IL-6 overproduction, uDkt. Kishimoto kunye neqela lakhe bazama ukunyanga izigulane ngokuthintela iimpawu ze-IL-6. Emva koko, i-tocilizumab, i-recombinant ye-anti-IL-6 receptor monoclonal antibody, yaphuhliswa ngempumelelo kwaye yamkelwa ukuba isetyenziswe kumazwe angaphezu kwe-100 kunyango lwe-rheumatoid arthritis kunye ne-JIA. Ngokumalunga nendlela ukuveliswa kwe-IL-6 kulawulwa ngayo kwaye kutheni i-IL-6 i-overproduction ivame ukuvela kwizifo ezingapheliyo ezivuthayo, uDkt Kishimoto wachaza ukuba ukuzinza kwe-IL-6 kuxhomekeke kakhulu kumthunywa wayo we-RNA. Ukuhlangula izigulana ezithwaxwa zizivunguvungu ze-cytokine ze-CAR-T, uninzi lwabasebenzi bezonyango ngoku baya kusebenzisa i-tocilizumab ukuthintela iziphumo ebezingalindelekanga zolu nyango. Ngokujonga lo mzekelo, uGqr. Kishimoto kunye neqela lakhe baqikelela ukuba i-tocilizumab inokusebenza ekuncedeni abaguli be-COVID-19 abagula kakhulu ukulwa nezaqhwithi ze-cytokine. Ulingo olukhulu lwekliniki lubonakalise ukuba lunokuthoba ukuba nokwenzeka kokufuna ukungena komoya okanye umngcipheko wokufa. Ngesi sizathu, uLawulo lokuTya kunye neChiza e-US kunye noMbutho wezeMpilo weHlabathi bobabini bakhuphe isiGunyaziso sokuSetyenziswa okuNgxamisekileyo kwi-tocilizumab kunyango lwe-COVID-19 yezigulana. Kule ntetho, uDkt. Kishimoto usinike inkcazo ebanzi yophando kwi-IL-6 wayekhokela iqela lakhe ekuqhubeni kwiminyaka eyi-50 edlulileyo. Yayiluhambo olwabathatha kuphando olusisiseko ukuya kuphuhliso lwamachiza kunye nesicelo seklinikhi.
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