Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy
ObjectiveSeveral 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984098/full |
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| author | Saeid Najafi-Fard Elisa Petruccioli Chiara Farroni Linda Petrone Valentina Vanini Valentina Vanini Gilda Cuzzi Andrea Salmi Anna Maria Gerarda Altera Assunta Navarra Tonino Alonzi Emanuele Nicastri Fabrizio Palmieri Gina Gualano Valentina Carlini Douglas McClain Noonan Douglas McClain Noonan Adriana Albini Delia Goletti |
| author_facet | Saeid Najafi-Fard Elisa Petruccioli Chiara Farroni Linda Petrone Valentina Vanini Valentina Vanini Gilda Cuzzi Andrea Salmi Anna Maria Gerarda Altera Assunta Navarra Tonino Alonzi Emanuele Nicastri Fabrizio Palmieri Gina Gualano Valentina Carlini Douglas McClain Noonan Douglas McClain Noonan Adriana Albini Delia Goletti |
| author_sort | Saeid Najafi-Fard |
| collection | DOAJ |
| description | ObjectiveSeveral 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.MethodsTwo 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.ResultsBaseline 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.ConclusionThis 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. |
| first_indexed | 2024-04-12T05:05:33Z |
| format | Article |
| id | doaj.art-01227a30aa924204992c1c64c978e6ea |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T05:05:33Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-01227a30aa924204992c1c64c978e6ea2022-12-22T03:46:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.984098984098Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapySaeid Najafi-Fard0Elisa Petruccioli1Chiara Farroni2Linda Petrone3Valentina Vanini4Valentina Vanini5Gilda Cuzzi6Andrea Salmi7Anna Maria Gerarda Altera8Assunta Navarra9Tonino Alonzi10Emanuele Nicastri11Fabrizio Palmieri12Gina Gualano13Valentina Carlini14Douglas McClain Noonan15Douglas McClain Noonan16Adriana Albini17Delia Goletti18Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Epidemiology and Preclinical Research, UOS Professioni Sanitarie Tecniche National Institute for Infectious Diseases Lazzaro Spallanzani-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyClinical Epidemiology Unit, National Institute for Infectious Disease Lazzaro Spallanzani-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyClinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyRespiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyRespiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyUnit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, ItalyUnit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, ItalyImmunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyEuropean Institute of Oncology IEO-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyObjectiveSeveral 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.MethodsTwo 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.ResultsBaseline 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.984098/fullCOVID-19SARS-CoV-2spikeIL-10whole-bloodNatutal Killer Cells |
| spellingShingle | Saeid Najafi-Fard Elisa Petruccioli Chiara Farroni Linda Petrone Valentina Vanini Valentina Vanini Gilda Cuzzi Andrea Salmi Anna Maria Gerarda Altera Assunta Navarra Tonino Alonzi Emanuele Nicastri Fabrizio Palmieri Gina Gualano Valentina Carlini Douglas McClain Noonan Douglas McClain Noonan Adriana Albini Delia Goletti Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy Frontiers in Immunology COVID-19 SARS-CoV-2 spike IL-10 whole-blood Natutal Killer Cells |
| title | Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy |
| title_full | Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy |
| title_fullStr | Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy |
| title_full_unstemmed | Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy |
| title_short | Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy |
| title_sort | evaluation of the immunomodulatory effects of interleukin 10 on peripheral blood immune cells of covid 19 patients implication for covid 19 therapy |
| topic | COVID-19 SARS-CoV-2 spike IL-10 whole-blood Natutal Killer Cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984098/full |
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