{"doi":"10.4049/jimmunol.2300426","title":"Plitidepsin as an Immunomodulator against Respiratory Viral Infections","abstract":"Plitidepsin 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 effect, but also for its immunomodulatory effect, both of which were evidenced in vitro and in vivo by the decrease of proinflammatory cytokines.","journal":"The Journal of Immunology","year":2024,"id":455418,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":312203,"name":"Nuria Izquierdo‐Useros","orcid":"0000-0002-1039-1821","position":1,"is_corresponding":false},{"id":1279230,"name":"Pablo Aviles","orcid":"0000-0001-7922-6042","position":2,"is_corresponding":false},{"id":218438,"name":"Júlia Vergara‐Alert","orcid":"0000-0001-7484-444X","position":3,"is_corresponding":false},{"id":1279231,"name":"Irene Latino","orcid":"0000-0002-4026-7071","position":4,"is_corresponding":false},{"id":218445,"name":"Joaquím Segalés","orcid":"0000-0002-1539-7261","position":5,"is_corresponding":false},{"id":14364,"name":"Santiago González","orcid":"0000-0003-4166-7664","position":6,"is_corresponding":false},{"id":1279232,"name":"Carmen Cuevas","orcid":"0000-0002-9116-2405","position":7,"is_corresponding":false},{"id":653884,"name":"Dàlia Raϊch‐Regué","orcid":"0000-0001-7656-5700","position":8,"is_corresponding":false},{"id":1279589,"name":"María José Muñoz-Alonso","orcid":null,"position":9,"is_corresponding":false},{"id":653880,"name":"Daniel Perez‐Zsolt","orcid":"0000-0003-4192-7622","position":10,"is_corresponding":false},{"id":653881,"name":"Jordana Muñoz‐Basagoiti","orcid":"0000-0002-0384-5928","position":11,"is_corresponding":false},{"id":653882,"name":"Jordi Rodon","orcid":"0000-0002-1032-9091","position":12,"is_corresponding":false},{"id":105591,"name":"Lauren A. Chang","orcid":"0000-0002-3287-3987","position":13,"is_corresponding":false},{"id":803942,"name":"Prajakta Warang","orcid":"0000-0002-5571-8277","position":14,"is_corresponding":false},{"id":803941,"name":"Gagandeep Singh","orcid":"0000-0003-3260-2631","position":15,"is_corresponding":false},{"id":499464,"name":"Marco Brustolin","orcid":"0000-0002-3594-4488","position":16,"is_corresponding":false},{"id":1279233,"name":"Guillermo Cantero","orcid":"0000-0003-4200-503X","position":17,"is_corresponding":false},{"id":1279234,"name":"Núria Roca","orcid":"0009-0009-7743-7458","position":18,"is_corresponding":false},{"id":1279590,"name":"Mónica Pérez","orcid":null,"position":19,"is_corresponding":false},{"id":758619,"name":"Eugenio Bustos‐Morán","orcid":"0000-0002-1160-231X","position":20,"is_corresponding":false},{"id":1481,"name":"Kris M. White","orcid":"0000-0003-0889-0506","position":21,"is_corresponding":false},{"id":107923,"name":"Michael Schotsaert","orcid":"0000-0003-3156-3132","position":22,"is_corresponding":false},{"id":1489,"name":"Adolfo Garcı́a-Sastre","orcid":"0000-0002-6551-1827","position":23,"is_corresponding":false},{"id":618029,"name":"Alejandro Losada","orcid":"0009-0001-2405-878X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"38416036","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}