{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:08:58Z","timestamp":1779448138489,"version":"3.53.1"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Bronchopulmonary dysplasia (BPD) remains a major complication of extreme prematurity, driven in part by persistent inflammation. Interleukin (IL)-1\u2013mediated signaling plays a central role in sustaining lung injury, making IL-1 blockade a potential therapeutic target. Evidence on the use of anakinra, a recombinant IL-1 receptor antagonist, in neonatal BPD is still limited. We report the case of a female preterm infant (28+2 weeks\u2019 gestation, birth weight 800 g, \u22121.41 zs) affected by BPD requiring prolonged respiratory support. Due to persistent respiratory failure despite standard therapies, off-label treatment with subcutaneous anakinra (5 mg\/kg twice daily) was initiated at 150 days of life. Clinical respiratory parameters and exploratory salivary inflammatory biomarkers (IL-6 and soluble urokinase plasminogen activator receptor, suPAR) were longitudinally monitored. Following anakinra initiation, the patient showed a gradual improvement in respiratory parameters, with reduction in oxygen requirement, mean airway pressure, and improved gas exchange. Respiratory support was gradually de-escalated from nasal intermittent positive pressure ventilation to continuous positive airway pressure and subsequently to high-flow nasal cannula. Salivary suPAR levels demonstrated a decreasing trend, while IL-6 showed transient fluctuations, partly associated with intercurrent infections. Treatment was generally well tolerated during the observation period. The infant was discharged on minimal respiratory support, with continued improvement during follow-up. This case suggests a possible role of IL-1 blockade in the modulation of persistent inflammation in BPD with a refractory clinical course, although the observed clinical course may also reflect the natural evolution of the disease. Longitudinal salivary biomarkers may represent a feasible, exploratory, non-invasive approach to describe inflammatory dynamics over time. Larger prospective studies are needed to evaluate the efficacy, safety, and optimal treatment protocols of anakinra.<\/jats:p>","DOI":"10.3390\/children13060717","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:07:47Z","timestamp":1779444467000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anakinra in a Preterm Infant with Bronchopulmonary Dysplasia: A Case Report"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2991-2068","authenticated-orcid":false,"given":"Simona","family":"Fattore","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9191-4219","authenticated-orcid":false,"given":"Chiara","family":"Tirone","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8914-8639","authenticated-orcid":false,"given":"Alessandro","family":"Perri","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Paola","family":"Fusco","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Frezza","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Women and Child Health Sciences, Child Health Area, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Tana","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7779","authenticated-orcid":false,"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[{"name":"Department of Women and Child Health Sciences, Child Health Area, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"},{"name":"Division of Pediatrics, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"De Tomaso","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8023-167X","authenticated-orcid":false,"given":"Nicoletta","family":"Menzella","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Lio","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-1469","authenticated-orcid":false,"given":"Francesca","family":"Serrao","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-1485","authenticated-orcid":false,"given":"Stefano","family":"Nobile","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Piras","sequence":"additional","affiliation":[{"name":"U.O.C. Farmacia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8528-7533","authenticated-orcid":false,"given":"Silvia","family":"Baroni","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-5297","authenticated-orcid":false,"given":"Simonetta","family":"Costa","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, Policlinico Casilino, 00169 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-9569","authenticated-orcid":false,"given":"Giovanni","family":"Vento","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Women and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Women and Child Health Sciences, Child Health Area, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tana, M., Tirone, C., Aurilia, C., Lio, A., Paladini, A., Fattore, S., Esposito, A., De Tomaso, D., and Vento, G. (2023). Respiratory management of the preterm infant: Supporting evidence-based practice at the bedside. Children, 10.","DOI":"10.3390\/children10030535"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151891","DOI":"10.1016\/j.semperi.2024.151891","article-title":"Long-term outcomes of infants with severe BPD","volume":"48","author":"Collaco","year":"2024","journal-title":"Semin. Perinatol."},{"key":"ref_3","first-page":"23","article-title":"Neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD)\u2014A retrospective cohort study","volume":"50","author":"Nguyen","year":"2024","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dankhara, N., Holla, I., Ramarao, S., and Kalikkot Thekkeveedu, R. (2023). Bronchopulmonary dysplasia: Pathogenesis and pathophysiology. J. Clin. Med., 12.","DOI":"10.20944\/preprints202305.0591.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1164\/rccm.201611-2386ED","article-title":"The evolution of bronchopulmonary dysplasia after 50 years","volume":"195","author":"Abman","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00134-006-0138-1","article-title":"Serum levels of seven cytokines in premature ventilated newborns: Correlations with old and new forms of bronchopulmonary dysplasia","volume":"32","author":"Vento","year":"2006","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.rmed.2017.10.014","article-title":"Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology","volume":"132","author":"Guaman","year":"2017","journal-title":"Respir. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1136\/thoraxjnl-2020-216485","article-title":"Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: A systematic review, meta-analysis and meta-regression","volume":"77","author":"Pierro","year":"2022","journal-title":"Thorax"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2101766","DOI":"10.1183\/13993003.01766-2021","article-title":"Association of early-life factors with prematurity-associated lung disease: Prospective cohort study","volume":"59","author":"Hart","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/s41372-021-01083-w","article-title":"Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia","volume":"41","author":"Htun","year":"2021","journal-title":"J. Perinatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s12016-007-8031-4","article-title":"Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia","volume":"34","author":"Ryan","year":"2008","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/AOG.0000000000001246","article-title":"Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: Summary of a workshop","volume":"127","author":"Higgins","year":"2016","journal-title":"Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s10020-024-00909-5","article-title":"Fetal origin of bronchopulmonary dysplasia: Contribution of intrauterine inflammation","volume":"30","author":"Yu","year":"2024","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1053\/j.semperi.2018.09.009","article-title":"Modulators of inflammation in bronchopulmonary dysplasia","volume":"42","author":"Savani","year":"2018","journal-title":"Semin. Perinatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1542\/peds.2010-3875","article-title":"Targeting inflammation to prevent bronchopulmonary dysplasia: Can new insights be translated into therapies?","volume":"128","author":"Wright","year":"2011","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8977","DOI":"10.1038\/ncomms9977","article-title":"The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia","volume":"6","author":"Liao","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L525","DOI":"10.1152\/ajplung.00067.2019","article-title":"Moderate hyperoxia induces senescence in developing human lung fibroblasts","volume":"317","author":"You","year":"2019","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1159\/000540002","article-title":"BPD: Latest Strategies of Prevention and Treatment","volume":"121","author":"Durlak","year":"2024","journal-title":"Neonatology"},{"key":"ref_19","first-page":"34","article-title":"Bronchopulmonary dysplasia: Pathophysiology and potential anti-inflammatory therapies","volume":"30","author":"Papagianis","year":"2019","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/1744666X.2017.1280396","article-title":"A systematic approach to autoinflammatory syndromes: A spelling booklet for the beginner","volume":"13","author":"Rigante","year":"2017","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s40272-024-00679-x","article-title":"Off-Label Use of Anakinra in Inflammatory Conditions in Neonates and Infants Up to 3 Months of Age: A Case Series and a Review of the Literature","volume":"27","author":"Campi","year":"2025","journal-title":"Paediatr. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Green, E.A., Metz, D., Galinsky, R., Atkinson, R., Skuza, E.M., Clark, M., Gunn, A.J., Kirkpatrick, C.M., Hunt, R.W., and Berger, P.J. (2022). Anakinra pilot\u2014A clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1022104"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1155\/2009\/504294","article-title":"suPAR: The molecular crystal ball","volume":"27","author":"Macho","year":"2009","journal-title":"Dis. Markers"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kany, S., Vollrath, J.T., and Relja, B. (2019). Cytokines in Inflammatory Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236008"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S630","DOI":"10.1016\/j.ajog.2018.01.011","article-title":"The INTERGROWTH-21st fetal growth standards: Toward the global integration of pregnancy and pediatric care","volume":"218","author":"Papageorghiou","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1164\/rccm.201812-2348OC","article-title":"The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach","volume":"200","author":"Jensen","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s00381-006-1280-3","article-title":"Hydrocephalus in CINCA syndrome treated with anakinra","volume":"22","author":"Rigante","year":"2006","journal-title":"Childs Nerv. Syst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"288","DOI":"10.63032\/TEVI1838","article-title":"Anakinra as a first-line therapy for systemic juvenile idiopathic arthritis when nonsteroidal anti-inflammatory drug treatment fails: A single-center French retrospective study","volume":"3","author":"Granel","year":"2024","journal-title":"ARP Rheumatol."},{"key":"ref_29","first-page":"301","article-title":"Current recommendations for the pharmacologic therapy in Kawasaki syndrome and management of its cardiovascular complications","volume":"11","author":"Pardeo","year":"2007","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"L285","DOI":"10.1152\/ajplung.00446.2010","article-title":"Pulmonary and systemic inflammatory responses to intra-amniotic IL-1alpha in fetal sheep","volume":"301","author":"Kallapur","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1159\/000028329","article-title":"Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized trial","volume":"59","author":"Romagnoli","year":"1999","journal-title":"Pharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Green, E.A., Garrick, S.P., Peterson, B., Berger, P.J., Galinsky, R., Hunt, R.W., Cho, S.X., Bourke, J.E., Nold, M.F., and Nold-Petry, C.A. (2023). The role of the Interleukin-1 family in complications of prematurity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032795"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41372-025-02275-4","article-title":"Dynamic association between plasma interleukin-1 family concentrations and bronchopulmonary dysplasia in extremely premature infants","volume":"46","author":"Li","year":"2026","journal-title":"J. Perinatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tao, X., Mo, L., and Zeng, L. (2022). Hyperoxia Induced Bronchopulmonary Dysplasia-Like Inflammation via miR34a-TNIP2-IL-1\u03b2 Pathway. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.805860"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1165\/rcmb.2016-0031OC","article-title":"Airway Remodeling and Hyperreactivity in a Model of Bronchopulmonary Dysplasia and Their Modulation by IL-1 Receptor Antagonist","volume":"55","author":"Royce","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14384","DOI":"10.1073\/pnas.1306859110","article-title":"Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia","volume":"110","author":"Nold","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cytogfr.2011.10.001","article-title":"Understanding the mechanism of IL-1\u03b2 secretion","volume":"22","author":"Brough","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1182\/blood.V75.6.1305.1305","article-title":"Interleukin-1 induces interleukin-6 production in peripheral blood monocytes","volume":"75","author":"Tosato","year":"1990","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.jacc.2017.09.028","article-title":"Interleukin-1 Beta as a Target for Atherosclerosis Therapy: Biological Basis of CANTOS and Beyond","volume":"70","author":"Libby","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cca.2014.11.029","article-title":"Soluble urokinase-type plasminogen activator receptor (suPAR) as new biomarker of the prosthetic joint infection: Correlation with inflammatory cytokines","volume":"441","author":"Galliera","year":"2015","journal-title":"Clin. Chim. Acta"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/6\/717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:50:36Z","timestamp":1779447036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/6\/717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["children13060717"],"URL":"https:\/\/doi.org\/10.3390\/children13060717","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}