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Biomedicines
Volume 10
Issue 9
10.3390/biomedicines10092324
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Article

The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro

by
Amelia Barilli
1,
Rossana Visigalli
1,
Francesca Ferrari
1,
Giulia Recchia Luciani
1,
Maurizio Soli
2,
Valeria Dall’Asta
1,* and
Bianca Maria Rotoli
1
1
Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
2
Immunohematology and Transfusion Medicine, University Hospital of Parma, 43125 Parma, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2022, 10(9), 2324; https://doi.org/10.3390/biomedicines10092324
Submission received: 20 July 2022 / Revised: 9 September 2022 / Accepted: 13 September 2022 / Published: 19 September 2022
(This article belongs to the Special Issue Non-antiviral Agents for Treatment of COVID-19)
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Abstract

The purpose of this study was to examine the effect of the JAK-STAT inhibitor baricitinib on the inflammatory response of human monocyte-derived macrophages (MDM) and endothelial cells upon exposure to the spike S1 protein from SARS-CoV-2. The effect of the drug has been evaluated on the release of cytokines and chemokines from spike-treated MDM, as well as on the activation of endothelial cells (HUVECs) after exposure to conditioned medium collected from spike-activated MDM. Results obtained indicate that, in MDM, baricitinib prevents the S1-dependent phosphorylation of STAT1 and STAT3, along with the induction of IP-10- and MCP-1 secretion; the release of IL-6 and TNFα is also reduced, while all other mediators tested (IL-1β, IL-8, RANTES, MIP-1α and MIP-1β) are not modified. Baricitinib is, instead, poorly effective on endothelial activation when HUVECs are exposed to supernatants from S1-activated macrophages; the induction of VCAM-1, indeed, is not affected by the drug, while that of ICAM-1 is only poorly inhibited. The drug, however, also exerts protective effects on the endothelium by limiting the expression of pro-inflammatory mediators, specifically IL-6, RANTES and IP-10. No effect of baricitinib has been observed on IL-8 synthesis and, consistently, on neutrophils chemiotaxis. Our in vitro findings reveal that the efficacy of baricitinib is limited, with effects mainly focused on the inhibition of the IL-6-mediated inflammatory loop.
Keywords: baricitinib; chemokines; COVID-19; endothelium; immune innate cells; JAK-STAT; IL-8 baricitinib; chemokines; COVID-19; endothelium; immune innate cells; JAK-STAT; IL-8

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MDPI and ACS Style

Barilli, A.; Visigalli, R.; Ferrari, F.; Recchia Luciani, G.; Soli, M.; Dall’Asta, V.; Rotoli, B.M. The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro. Biomedicines 2022, 10, 2324. https://doi.org/10.3390/biomedicines10092324

AMA Style

Barilli A, Visigalli R, Ferrari F, Recchia Luciani G, Soli M, Dall’Asta V, Rotoli BM. The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro. Biomedicines. 2022; 10(9):2324. https://doi.org/10.3390/biomedicines10092324

Chicago/Turabian Style

Barilli, Amelia, Rossana Visigalli, Francesca Ferrari, Giulia Recchia Luciani, Maurizio Soli, Valeria Dall’Asta, and Bianca Maria Rotoli. 2022. "The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro" Biomedicines 10, no. 9: 2324. https://doi.org/10.3390/biomedicines10092324

APA Style

Barilli, A., Visigalli, R., Ferrari, F., Recchia Luciani, G., Soli, M., Dall’Asta, V., & Rotoli, B. M. (2022). The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro. Biomedicines, 10(9), 2324. https://doi.org/10.3390/biomedicines10092324

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