{"doi":"10.1093/infdis/jiae021","title":"Loratadine as an Anti-inflammatory Agent Against <i>Clostridium difficile</i> Toxin B","abstract":"BACKGROUND: Clostridium difficile infection (CDI) is a debilitating nosocomial infection. C. difficile produces toxins A and B, which cause inflammation. Existing therapies have issues with recurrence, cost, and safety. We aim to discover a safe, effective, and economical nonmicrobiological therapeutic approach against CDI. METHODS: We included human primary peripheral blood mononuclear cells (PBMCs), fresh human colonic explants, and humanized HuCD34-NCG mice. Toxin A+B+ VPI 10463 and A-B+ ribotype 017 C. difficile strains were used. We used single-cell RNA profiling and high-throughput screening to find actionable toxin B-dependent pathways in PBMCs. RESULTS: Histamine 1 receptor-related drugs were found among the hit compounds that reversed toxin-mediated macrophage inflammatory protein (MIP) 1α expression in PBMCs. We identified loratadine as the safest representative antihistamine for therapeutic development. Loratadine inhibited toxin B-induced MIP-1α secretion in fresh human colonic tissues. Oral loratadine (10 mg/kg/d) maintained survival, inhibited intestinal CCl3 messenger RNA expression, and prevented vancomycin-associated recurrence in the VPI 10463-infected mice and ribotype 017-infected hamsters. Splenocytes from loratadine-treated mice conferred anti-inflammatory effects to the VPI 10463-infected T/B-cell--deficient Rag-/- mice. Oral loratadine suppressed human MIP-1α expression in monocytes/macrophages in toxin B-expressing ribotype 017-infected humanized HuCD34-NCG mice. CONCLUSIONS: Loratadine may be repurposed to optimize existing therapies against CDI.","journal":"The Journal of Infectious Diseases","year":2024,"id":455199,"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":0.9683,"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":1279059,"name":"Sophie Irwin","orcid":"0000-0002-2821-8015","position":1,"is_corresponding":false},{"id":1072741,"name":"Andrea Chupina Estrada","orcid":"0000-0002-3331-0959","position":2,"is_corresponding":false},{"id":1072742,"name":"Becca Nelson","orcid":"0000-0001-7338-3215","position":3,"is_corresponding":false},{"id":1072743,"name":"Ashlen Bullock","orcid":"0000-0002-6258-7420","position":4,"is_corresponding":false},{"id":424049,"name":"Lindsey Fontenot","orcid":"0000-0002-7430-5275","position":5,"is_corresponding":false},{"id":776058,"name":"Hanping Feng","orcid":"0000-0002-8685-1812","position":6,"is_corresponding":false},{"id":1072744,"name":"Mingjun Sun","orcid":"0000-0001-8748-4658","position":7,"is_corresponding":false},{"id":424053,"name":"Hon Wai Koon","orcid":"0000-0003-0618-0869","position":8,"is_corresponding":false},{"id":424050,"name":"Ying Xie","orcid":"0000-0003-0620-1519","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"38243838","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":[]}