{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T07:51:06Z","timestamp":1764402666376,"version":"build-2065373602"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,9,7]],"date-time":"2015-09-07T00:00:00Z","timestamp":1441584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics\/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of  an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti-cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents.<\/jats:p>","DOI":"10.3390\/ijms160921277","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T11:59:54Z","timestamp":1441713594000},"page":"21277-21293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["To Extinguish the Fire from Outside the Cell or to Shutdown the Gas Valve Inside? Novel Trends in Anti-Inflammatory Therapies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3427-618X","authenticated-orcid":false,"given":"Annalisa","family":"Marcuzzi","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, Trieste 34128, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-1684","authenticated-orcid":false,"given":"Elisa","family":"Piscianz","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\" - , via dell'Istria, 65\/1,  Trieste 34137, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Valencic","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\" - , via dell'Istria, 65\/1,  Trieste 34137, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-548X","authenticated-orcid":false,"given":"Lorenzo","family":"Monasta","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\" - , via dell'Istria, 65\/1,  Trieste 34137, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liza","family":"Brumatti","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\" - , via dell'Istria, 65\/1,  Trieste 34137, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\" - , via dell'Istria, 65\/1,  Trieste 34137, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cyto.2015.02.012","article-title":"Monogenic autoinflammatory diseases: Cytokinopathies","volume":"74","author":"Moghaddas","year":"2015","journal-title":"Cytokine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cyto.2015.02.007","article-title":"B cells responses and cytokine production are regulated by their immune microenvironment","volume":"74","author":"Vazquez","year":"2015","journal-title":"Cytokine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nri2764","article-title":"Can primary immunodeficiencies help to provide insights into infectious risks of therapeutic antibodies?","volume":"10","author":"Casanova","year":"2010","journal-title":"Nat. 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