TY - JOUR
T1 - Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients
T2 - Implication for COVID-19 therapy
AU - Najafi-Fard, Saeid
AU - Petruccioli, Elisa
AU - Farroni, Chiara
AU - Petrone, Linda
AU - Vanini, Valentina
AU - Cuzzi, Gilda
AU - Salmi, Andrea
AU - Altera, Anna Maria Gerarda
AU - Navarra, Assunta
AU - Alonzi, Tonino
AU - Nicastri, Emanuele
AU - Palmieri, Fabrizio
AU - Gualano, Gina
AU - Carlini, Valentina
AU - Noonan, Douglas Mc Clain
AU - Albini, Adriana
AU - Goletti, Delia
N1 - Funding Information:
This work was supported by: Funding from Italian Ministry of Health Ricerca Finalizzata COVID-2020-12371849 (DN), 0000395 del 25/05/2021, COVID-2020-12371675, Ricerca Corrente funded COVID-2020-12371849 (DN), 0000395 del 25/05/2021, COVID-2020-12371675 Ricerca Corrente funded by Italian Ministry of Health, and by generous liberal donations funding for COVID-19 research from Esselunga S.p.A, Camera di Commercio, Industria e Artigianato di Roma, Società Numero Blu Servizi S.p.A., Fineco Bank S.p.A, Associazione magistrati della Corte dei conti, and Società Mocerino Frutta Secca s.r.l. (resolutions n°395 of May 25th 2021, n°254 of April 24th 2021 and n°257 of April 14th 2021). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Publisher Copyright:
Copyright © 2022 Najafi-Fard, Petruccioli, Farroni, Petrone, Vanini, Cuzzi, Salmi, Altera, Navarra, Alonzi, Nicastri, Palmieri, Gualano, Carlini, Noonan, Albini and Goletti.
PY - 2022/9/6
Y1 - 2022/9/6
N2 - Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform. Methods: Two cohorts were evaluated: in “study population A”, plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized “COVID-19 patients” and 29 “NO COVID-19 controls” all unvaccinated. In “study population B”, 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis. Results: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in “study population A”. Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in “study population B”. Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8+ and NK cells. Conclusion: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.
AB - Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform. Methods: Two cohorts were evaluated: in “study population A”, plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized “COVID-19 patients” and 29 “NO COVID-19 controls” all unvaccinated. In “study population B”, 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis. Results: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in “study population A”. Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in “study population B”. Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8+ and NK cells. Conclusion: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.
KW - COVID-19
KW - cytokine
KW - IL-10
KW - Natutal Killer Cells
KW - SARS-CoV-2
KW - spike
KW - T cell
KW - whole-blood
UR - http://www.scopus.com/inward/record.url?scp=85138408295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138408295&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.984098
DO - 10.3389/fimmu.2022.984098
M3 - Article
C2 - 36148228
AN - SCOPUS:85138408295
SN - 1664-3224
VL - 13
SP - 1
EP - 17
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 984098
ER -