Plitidepsin as an Immunomodulator against Respiratory Viral Infections
J Immunol. 2024 Feb 28:ji2300426. doi: 10.4049/jimmunol.2300426. Online ahead of print.ABSTRACTPlitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimulated THP1 human monocytes, plitidepsin-mediated reductions of IL-6 mRNA and IL-6 levels were also noticed. Additionally, although resiquimod-induced binding to DNA of NF-κB family members was unaffected by plitidepsin, a decrease in the regulated transcription by NF-κB (a key transcription factor involved in the inflammatory cascade) was observed. Furthermore, the phosphorylation of p65 that is required for full transcriptional NF-κB activity was significantly reduced by plitidepsin. Moreover, decreases of IL-6 levels and other proinflammatory cytokines were also seen in either SARS-CoV-2 or H1N1 influenza virus-infected mice, which were treated at low enough plitidepsin doses to not induce antiviral effects. In summary, plitidepsin is a promising therapeutic agent for the treatment of viral infections, not only because of its host-targeted antiviral eff...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Alejandro Losada Nuria Izquierdo-Useros Pablo Aviles J úlia Vergara-Alert Irene Latino Joaquim Segal és Santiago F Gonzalez Carmen Cuevas D àlia Raïch-Regué Mar ía J Muñoz-Alonso Daniel Perez-Zsolt Jordana Mu ñoz-Basagoiti Jordi Rodon Lauren A Cha Source Type: research