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1.
Cell Rep ; 37(5): 109942, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: covidwho-1471904

RESUMEN

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , COVID-19/prevención & control , SARS-CoV-2/inmunología , Envejecimiento/inmunología , Animales , COVID-19/líquido cefalorraquídeo , COVID-19/complicaciones , COVID-19/inmunología , Complicaciones de la Diabetes/inmunología , Complicaciones de la Diabetes/virología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/inmunología , Femenino , Humanos , Activación de Linfocitos , Macaca mulatta , Masculino , Neuritis/inmunología , Neuritis/prevención & control , Profilaxis Pre-Exposición , Linfocitos T/inmunología , Replicación Viral/inmunología
2.
Int J Immunopathol Pharmacol ; 35: 20587384211005645, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1156054

RESUMEN

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F ß-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , MAP Quinasa Quinasa 4/metabolismo , FN-kappa B/metabolismo , Peroxiredoxina VI , Transducción de Señal , Factor Tímico Circulante , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , COVID-19/inmunología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/inmunología , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Descubrimiento de Drogas , Interferón gamma/sangre , Interleucinas/sangre , Ratones , Peroxiredoxina VI/metabolismo , Peroxiredoxina VI/farmacología , SARS-CoV-2 , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Factor Tímico Circulante/metabolismo , Factor Tímico Circulante/farmacología , Factor de Necrosis Tumoral alfa/sangre
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