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Ka maʻi maʻi a me ka noiʻi COVID: ʻO ke kuleana o nā Cytokines

i kakauia ma ʻO Linda S. Hohnholz

Ma hope o ka haʻiʻōlelo hoʻomaka ʻana, "Future Perspective of Cancer Immunotherapy," i hāʻawi ʻia e ka makana Nobel a me ka makana Tang Prize laureate Prof. Tasuku Honjo ma ka 14th Asia Pacific Federation of Pharmacologist Conference (APFP) ma Nowemapa 26, ka 2020 Tang Prize Laureate's Lecture for Biopharmaceutical ʻEpekema, i hui pū ʻia e ka Tang Prize Foundation a me The Pharmacological Society ma Taiwan, i mālama ʻia ma ka 14th APFP ma 1:30 pm (GMT+8) ma Nowemapa 27.

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Hoʻokipa pū ʻia e Dr. Wen-Chang Chang, ka luna o ka papa alakaʻi o ke Kulanui Lapaʻau o Taipei, a me Kauka Yun Yen, ka luna kaukaʻi ma ke Kulanui Lapaʻau ʻo Taipei, ua hōʻike ʻia kēia kau kūikawā i nā haʻiʻōlelo i hāʻawi ʻia e ʻekolu mau lanakila no ka makana Tang 2020 ma Biopharmaceutical Science. , Ua haʻi aku ʻo Dr. ʻO Charles Dinarello, ʻo Marc Feldmann, a me Tadamitsu Kishimoto, e hāʻawi ana i ka ʻike koʻikoʻi e pili ana i ka hana o nā cytokines e pāʻani ai i ka mumū a me ka maʻi COVID-19 a me nā lāʻau lapaʻau.

ʻO ka haʻiʻōlelo mua a Dr. Dinarello, i kapa ʻia ʻo "Interleukin-1: The Prime Mediator of Systemic and Local Inflammation," i hoʻomaka me kāna hoʻomaʻemaʻe ʻana i ka leukocytic pryogen mai nā keʻokeʻo keʻokeʻo kanaka ma 1971. A laila lawe ʻo ia iā ia i ʻeono makahiki e ʻike ai i ʻelua fever- e hana ana i nā molekala, i kapa ʻia ma hope aku ʻo IL-1α a me IL-1β. I ka makahiki 1977, ua paʻi ʻia nā hopena noiʻi ma ka Proceedings of the National Academy of Sciences, a no Dr. Dinarello, "he hana koʻikoʻi ia i ka mōʻaukala o ka biology cytokine," no ka mea, ua paipai ʻia nā poʻe he nui i ke kahua o ka ʻepekema ola. e aʻo i ka mana o ka ʻōnaehana pale i ka physiology kanaka. ʻO ka hopena, ua hoʻonui wikiwiki ka biology cytokine. Ua kamaʻilio pū ʻo ia e pili ana i ke ʻano ma hope o nā hoʻokolohua mua i nā kānaka, "ua loli nui ka mōʻaukala o nā cytokines i hoʻohana ʻia ma ke ʻano he lāʻau lapaʻau," a ua hoʻohuli ʻia ka manaʻo i ka "inhibiting cytokines, e like me IL-1, e like me TNF, e like me IL- 6.” No ke kōkua ʻana i ka poʻe e hoʻomaopopo i ka pūnaewele paʻakikī i hoʻokumu ʻia e nā molekele pro-inflammatory o ka ʻohana IL-1, ua wehewehe ʻo Dr. Dinarello i ka hoʻololi ʻana i ka hōʻailona o nā lālā o ka ʻohana IL-1, ko lākou mau ʻano pro-a anti-inflammatory, a me nā hōʻailona o nā maʻi ʻeha like ʻole, i mea e maʻalahi ai ke ala no ka poʻe e ʻike pono ai i ka hapa lua o ka haʻiʻōlelo i kau ʻia ma luna o "ka noi lapaʻau o Il-1 blockade." ʻO ka nui o ka IL-1, e like me kā Dr. Dinarello i ʻōlelo ai, he kumu maʻamau ia o nā maʻi he nui. ʻO IL-1Ra, ma ka ʻaoʻao ʻē aʻe, hiki ke kāohi iā Il-1αandβ, a pale i ka hōʻailona IL-1R. Ua hana ʻia ʻo Anakinra, kahi kanaka recombinant IL-1Ra. Hoʻohana ʻia ia e mālama i ka maʻi rheumatoid a hiki ke pale i nā maʻi glycemic i ka maʻi diabetes type 2. Eia kekahi, ua ʻae ʻia ʻo canakinumab, kahi anti-IL-1βmonoclonal antibody i hoʻomohala maikaʻi ʻia e Novartis, i nā maʻi like ʻole, mai nā maʻi hoʻoilina liʻiliʻi, nā maʻi rheumatic, nā maʻi autoimmune a me nā maʻi inflammatory, i nā maʻi cardiovascular. ʻO ka nūhou hauʻoli loa e pili ana i ka canakinumab ʻo ia ka hoʻokolohua lapaʻau, ʻo CANTOS, ka mea i hōʻike ʻole ʻia he kuleana ko ka canakinumab i ka mālama ʻana i ka maʻi kanesa. No laila, manaʻoʻiʻo ʻo Dr. Dinarello ʻo ka pale ʻana i ka IL-1 hiki ke hoʻomaka i ka wanaʻao o kahi lāʻau lapaʻau hou.

ʻO ka lua o ka haʻi'ōlelo,ʻo Dr. Feldmann, i haʻi aku i kāna mau manaʻo ma "Translating Molecular Insights in Autoimmunity into Effective Therapy." ʻO ka manaʻo nui o ka hapa mua o kāna aʻo ʻana ʻo ia ka mea i ʻike ai he hiki i ka anti-TNF ke kūpono i ka mālama ʻana i ka maʻi rumatika. ʻO ka hoʻokele ʻana i nā haʻahaʻa kiʻekiʻe a haʻahaʻa paha o kēia lāʻau lapaʻau hiki ke kāohi iā TNF me ka hoʻohaʻahaʻa wikiwiki ʻana i ka hana ʻana o nā mea hoʻomohala ʻē aʻe. I kā lākou mau hoʻokolohua mua, ua hōʻike ʻo Kauka Feldmann a me kāna hui ma kahi o 50% o ka poʻe me ka rheumatoid arthritis i pane i ka hui pū ʻana me ka anti-TNF a me ka lāʻau lapaʻau methotrexate. Ua alakaʻi iā ia e manaʻoʻiʻo "he lōʻihi kā mākou e hele ai ma mua o ka hoʻōla ʻana o kēlā me kēia maʻi." I ka hapa lua o ke kamaʻilio ʻana, ua haʻi mai ʻo Kauka Feldmann iā mākou "He mea noʻonoʻo maʻamau ʻo TNF, no ka mea, ʻelua mau pahuhopu ʻokoʻa: TNF receptor-1(TNFR1), ka mea e hoʻoulu ai i ka mumū, a me ka TNF receptor 2, ka mea e hana ai kūʻē. No laila inā pale ʻoe i nā TNF āpau, poloka ʻoe i nā mea loaʻa. Paʻa ʻoe i ka ʻāʻī, akā pale pū ʻoe i ka hoʻāʻo ʻana o ke kino e hoʻohaʻahaʻa i ka mumū. No laila, ʻo ia a me kāna mau hoa hana "i ke kaʻina hana o ka hana ʻana i nā mea hana" a ua pāpā mua iā TNFR1 me ka ʻole o ka hoʻololi ʻana i ka hana o nā pūnaewele T regulatory. Eia hou, ua'ōleloʻo Dr. Feldmann i ka hiki o ka anti-TNF no ka hoʻoponoponoʻana i nā pono olakino he nuiʻole, e like me ka mālamaʻana i ka fibrosis o ka lima ma ka hoʻokomoʻana i ka anti-TNF i loko o ka poho lima. Eia naʻe, ua kuhikuhi ʻo ia i nā hemahema ʻelua o ka anti-TNF āna i hoʻomohala mua ai: ʻo ia ke kumu kūʻai a "he lāʻau injectable." No laila, ʻo ka hoʻomohala ʻana i nā "lāʻau lapaʻau ʻoi aku ka maikaʻi i hiki ke hāʻawi ʻia ma ka waha" e lawe mai i ka pōmaikaʻi nui i ka lehulehu. I loko o ke aʻo ʻana, ua hoʻomau ʻo Kauka Feldmann i ka hāpai ʻana i nā poʻe he nui me ia a i ʻole e hui pū nei no nā papahana like ʻole a me nā hoʻokolohua, ʻoiai ʻo ia i hoʻāʻo e hoʻihoʻi i ka home i ka ʻōlelo ʻo kāna mea i aʻo ai mai kēia mau ʻike ʻo "pehea e hana pono ai me nā poʻe ʻē aʻe" e hōʻoia i ka holomua mau i kā lākou noiʻi. ʻO ia ka hōʻailona o kāna ʻoihana ka loaʻa ʻana o "ka poʻe akamai e hana pū me," a, "me lākou," e hoʻokō i nā mea ʻoi aku "ma mua o ka hiki iā mākou wale nō."

Ke hōʻike nei i ke kolu o ka haʻi'ōlelo ma ke kumuhana "Interleukin-6: Mai Arthritis a CAR-T a me COVID-19," ua huki ʻo Kauka Kishimoto i ka manaʻo o ka poʻe i ka ʻike ʻia ʻana o IL-6, no ke aha he mole pleiotropic ʻo IL-6, a no ke aha. ʻO IL-6 "ke kuleana no ka hana ʻana o ka antibody a me ka hoʻoulu ʻana i ka mumū." Ua hoʻomālamalama ʻo ia i nā hopena o IL-6 i nā maʻi autoimmune a pehea e hiki ai iā IL-6 ke hoʻoulu i nā ʻino cytokine. I ka hoʻomaka ʻana o kāna kamaʻilio ʻana, ua wehewehe ʻo Kauka Kistimoto i ka hoʻonui ʻana o ka IL-6 i ʻike ʻia e pili ana me nā maʻi he nui, e like me ka myxoma cardiac, Castleman's disease, rheumatoid arthritis, a me ka hoʻomaka ʻana o ka juvenile idiopathic arthritis (JIA). No ka hoʻoponopono ʻana i nā pane ʻino i hoʻonāukiuki ʻia e ka overproduction o IL-6, ua hoʻāʻo ʻo Kauka Kishimoto a me kāna hui e mālama i nā maʻi ma ke kāohi ʻana i nā hōʻailona IL-6. Ma hope mai, ua hoʻomohala maikaʻi ʻia ʻo tocilizumab, kahi recombinant humanized anti-IL-6 receptor monoclonal antibody, a ua ʻae ʻia no ka hoʻohana ʻana ma mua o 100 mau ʻāina no ka mālama ʻana i ka rheumatoid arthritis a me JIA. E pili ana i ke ʻano o ka hoʻoponopono ʻia ʻana o ka hana ʻana o IL-6 a no ke aha e ulu pinepine ai ka overproduction o IL-6 i nā maʻi inflammatory mau, ua wehewehe ʻo Kauka Kishimoto i ka hilinaʻi ʻana o ka IL-6 i kāna ʻelele RNA. No ka hoʻopakele ʻana i nā maʻi e loaʻa ana i nā ʻino cytokine CAR-T cell-induced, nui ka poʻe i ka ʻoihana lapaʻau i kēia manawa e hoʻohana i ka tocilizumab e hoʻopau i nā hopena ʻaoʻao o kēia lāʻau. I ka nānā ʻana i kēia hiʻohiʻona, ua kuhi ʻo Kauka Kishimoto a me kāna hui e hiki nō hoʻi i ka tocilizumab ke kōkua i ke kōkua ʻana i nā mea maʻi maʻi COVID-19 e hakakā i nā ʻino cytokine. Ua hōʻike ʻia kekahi mau hoʻokolohua lapaʻau nui e hiki ke hoʻohaʻahaʻa i ka hiki ke koi ʻia ka invasive ventilation a i ʻole ka pilikia o ka make. No kēia kumu, ua hoʻopuka ka US Food and Drug Administration a me ka World Health Organization i kahi Mana Hoʻohana Emergency no tocilizumab no ka mālama ʻana i nā maʻi maʻi COVID-19. Ma kēia haʻiʻōlelo, ua hāʻawi mai ʻo Kauka Kishimoto iā mākou i kahi ʻike piha o ka noiʻi ʻana ma IL-6 āna i alakaʻi ai i kāna hui i ka hoʻokō ʻana i nā makahiki he 50 i hala. He huakaʻi ia i lawe iā lākou mai ka noiʻi kumu i ka hoʻomohala ʻana i ka lāʻau lapaʻau a me ka noi lapaʻau.

ʻO kēia mau haʻiʻōlelo ʻekolu e ka 2020 Tang Prize laureates ma Biopharmaceutical Science e hoʻomaka mua ʻia ma ka Tang Prize YouTube channel mai 4 pm a 7 pm (GMT+8) ma Nowemapa 27.

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ʻO Linda S. Hohnholz

ʻO Linda Hohnholz ka luna hoʻoponopono no eTurboNews no nā makahiki he nui.
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