{"doi":"10.1093/infdis/jiaf148","title":"Interleukin 8 as a Causal Link Between Aging and Impaired Influenza Antibody Responses in Older Adults","abstract":"BACKGROUND: Antibody responses to MF59-adjuvanted (MF59Flu) and high-dose (HDFlu) influenza vaccines have been well-characterized in older adults, yet corresponding cellular immune response data remain limited. METHODS: Blood samples were collected from 106 MF59Flu recipients and 112 HDFlu recipients at 4 time points: before vaccination (day 0) and on days 1, 8, and 28 postvaccination. Antibody responses were assessed in serum samples using a hemagglutination inhibition assay. Eight proinflammatory cytokines and chemokines, including IFN-α2a, IFN-γ, IP-10, MCP-1, MIP-1α, IL-1β, IL-6, and IL-8, were quantified from peripheral blood mononuclear cells using a multiplex assay. Associations between cytokine/chemokine secretion levels and antibody responses were examined, along with the effect of sex, age, body mass index (BMI), and cytomegalovirus infection status. RESULTS: Age was positively correlated with IL-8 levels on day 1 (r = 0.24, P < .001) and the change in IL-8 levels from day 0 to day 1 (r = 0.16, P = .021). Notably, the change in IL-8 levels was negatively associated with day 28 hemagglutination inhibition titers (r = -0.15, P = .026). Causal mediation analysis demonstrated that IL-8 exerted significant causal mediation effects on antibody responses at both day 8 (P = .046) and day 28 (P = .0045). No significant effects of other cytokines and chemokines, vaccine type, sex, or BMI on antibody responses were observed. CONCLUSIONS: Our findings underscore IL-8 as a potential mediator of antibody responses to influenza vaccination in older adults, suggesting that IL-8 inhibition could serve as a molecular intervention to improve antibody responses in this high-risk population.","journal":"The Journal of Infectious Diseases","year":2025,"id":563112,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":705508,"name":"Krista M. Goergen","orcid":null,"position":1,"is_corresponding":false},{"id":584375,"name":"Diane E. Grill","orcid":"0000-0002-8677-1724","position":2,"is_corresponding":false},{"id":275824,"name":"Inna G. Ovsyannikova","orcid":"0000-0003-1506-9214","position":3,"is_corresponding":false},{"id":275825,"name":"Gregory A. Poland","orcid":"0000-0001-5057-4457","position":4,"is_corresponding":false},{"id":275823,"name":"Richard B. Kennedy","orcid":"0000-0001-6164-4967","position":5,"is_corresponding":false},{"id":916316,"name":"Huy Quang Quach","orcid":"0000-0003-2191-5771","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:56:13.374766Z","pmid":"40091229","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":[]}