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Interleukin-6 (IL-6), a pleiotropic cytokine implicated in both Type 2-low airway inflammation and radon-related lung carcinogenesis, may represent a key mechanistic link between radon exposure and asthma morbidity. We aimed to evaluate the association between indoor radon exposure and plasma IL-6 levels in children with asthma and whether this relationship differs by allergic sensitization status. Methods: We analyzed baseline data from the School Inner-City Asthma Study, a prospective cohort of children aged 4\u201313 years with persistent asthma. Monthly indoor radon concentrations at each participant\u2019s residential ZIP Code Tabulation Area were estimated using a validated spatiotemporal prediction model. Plasma IL-6 was measured from baseline blood samples. Multivariable linear mixed-effects models with random intercepts for school were used to assess the association between radon exposure and IL-6, adjusting for demographic, clinical, and socioeconomic covariates. Effect modification by allergic sensitization was evaluated using an interaction term. Results: Among 144 participants, 62.5% were allergen-sensitized. The median home radon concentration was 46.6 Bq\/m3 (range 30.7\u201399.9), and the mean plasma IL-6 was 0.22 pg\/mL (SD 0.41). A significant interaction was observed between radon exposure and allergic sensitization status (\u03b2-interaction = \u22120.012; p = 0.014), indicating differential effects by phenotype. Among non-sensitized children, higher radon exposure was associated with increased IL-6 levels (\u03b2 = 0.0088; p = 0.044), corresponding to a 0.32 pg\/mL rise in IL-6 per 37 Bq\/m3 increase in radon. No significant association was observed among sensitized children. Conclusions: Indoor radon exposure is associated with higher plasma IL-6 levels in non-sensitized children with asthma, suggesting a potential IL-6\u2013mediated pathway linking radon exposure to asthma morbidity in the Type 2-low phenotype. These findings highlight heterogeneity in environmental asthma responses and support further investigation into radon mitigation as a modifiable factor to improve asthma outcomes. IL-6 may serve as a biomarker to identify children most susceptible to radon-related airway inflammation, guiding personalized mitigation strategies and targeted interventions to improve asthma outcomes. Future studies should incorporate direct home radon measurements, comprehensive endotyping panels, and longitudinal biomarker sampling to validate these findings and elucidate whether IL-6 trans-signaling pathways mediate radon-induced airway injury in non-allergic asthma.<\/jats:p>","DOI":"10.3390\/jpm16050245","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:50:01Z","timestamp":1777618201000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Plasma IL-6 with Indoor Radon Exposure in Children with Non-Allergic Asthma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6446-6789","authenticated-orcid":false,"given":"Saleh","family":"Alsulami","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-2618","authenticated-orcid":false,"given":"Youn Soo","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perdita","family":"Permaul","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Allergy and Immunology, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Koutrakis","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-4504","authenticated-orcid":false,"given":"Jonathan M.","family":"Gaffin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8639-0473","authenticated-orcid":false,"given":"Wanda","family":"Phipatanakul","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M.","family":"Banzon","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1016\/S2213-2600(25)00242-5","article-title":"2025 GINA report for asthma","volume":"13","author":"Venkatesan","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12016-018-8712-1","article-title":"Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease","volume":"56","author":"Kuruvilla","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2021.02.016","article-title":"The basic immunology of asthma","volume":"184","author":"Hammad","year":"2021","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S2213-2600(16)30048-0","article-title":"Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: A cross-sectional analysis of two cohorts","volume":"4","author":"Peters","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.7150\/ijbs.4874","article-title":"Role of IL-6 in Asthma and Other Inflammatory Pulmonary Diseases","volume":"8","author":"Rincon","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jaci.2018.05.026","article-title":"Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation","volume":"143","author":"Jevnikar","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"Bettelli","year":"2006","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.jaci.2021.12.769","article-title":"TH17 cells and corticosteroid insensitivity in severe asthma","volume":"149","author":"Xie","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","unstructured":"United States Environmental Protection Agency (2026, March 11). Radionuclide Basics: Radon, Available online: https:\/\/www.epa.gov\/radiation\/radionuclide-basics-radon."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Henyoh, A.M.S., Laurent, O., Mandin, C., and Clero, E. (2024). Radon exposure and potential health effects other than lung cancer: A systematic review and meta-analysis. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1439355"},{"key":"ref_11","unstructured":"WHO (2009). Guidelines Approved by the Guidelines Review Committee. WHO Handbook on Indoor Radon: A Public Health Perspective, World Health Organization."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7157","DOI":"10.1021\/acs.est.0c08792","article-title":"Predicting Monthly Community-Level Domestic Radon Concentrations in the Greater Boston Area with an Ensemble Learning Model","volume":"55","author":"Li","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103812","DOI":"10.1016\/j.etap.2022.103812","article-title":"Repeated radon exposure induced lung damage via oxidative stress-mediated mitophagy in human bronchial epithelial cells and mice","volume":"90","author":"Xin","year":"2022","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1289\/ehp.1409437","article-title":"Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners","volume":"124","author":"Leng","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.jaci.2025.01.033","article-title":"Biomarkers of inflammation associated with radon exposure in the School Inner-City Asthma Study (SICAS)","volume":"155","author":"Banzon","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1002\/ppul.26143","article-title":"Environmental radon and childhood asthma","volume":"57","author":"Mukharesh","year":"2022","journal-title":"Pediatr. Pulmonol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Taylor, B.K., Smith, O.V., and Miller, G.E. (2022). Chronic Home Radon Exposure Is Associated with Higher Inflammatory Biomarker Concentrations in Children and Adolescents. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20010246"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125748","DOI":"10.1016\/j.chemosphere.2019.125748","article-title":"Residential exposure to radon and levels of histone \u03b3H2AX and DNA damage in peripheral blood lymphocytes of residents of Kowary city regions (Poland)","volume":"247","author":"Walczak","year":"2020","journal-title":"Chemosphere"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cct.2017.06.008","article-title":"The School Inner-City Asthma Intervention Study: Design, rationale, methods, and lessons learned","volume":"60","author":"Phipatanakul","year":"2017","journal-title":"Contemp. Clin. Trials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2408084121","DOI":"10.1073\/pnas.2408084121","article-title":"High-resolution national radon maps based on massive indoor measurements in the United States","volume":"122","author":"Li","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1002\/ppul.26429","article-title":"Effect of radon exposure on asthma morbidity in the School Inner-City Asthma study","volume":"58","author":"Banzon","year":"2023","journal-title":"Pediatr. Pulmonol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.jaci.2023.06.027","article-title":"High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children","volume":"152","author":"Greco","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12931-023-02617-w","article-title":"An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma","volume":"24","author":"Khalenkow","year":"2023","journal-title":"Respir. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17281","DOI":"10.1073\/pnas.1202244109","article-title":"Early environments and the ecology of inflammation","volume":"109","author":"McDade","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/all.15606","article-title":"Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL-6-mediated protection associated with cecal microbiota changes","volume":"78","author":"Gao","year":"2023","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1165\/rcmb.2015-0084OC","article-title":"Urban Particulate Matter\u2013Activated Human Dendritic Cells Induce the Expansion of Potent Inflammatory Th1, Th2, and Th17 Effector Cells","volume":"54","author":"Matthews","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/5\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:12:22Z","timestamp":1778731942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/5\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jpm16050245"],"URL":"https:\/\/doi.org\/10.3390\/jpm16050245","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}