{"id":25851,"date":"2025-02-28T12:59:36","date_gmt":"2025-02-28T11:59:36","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/02\/28\/development-of-anti-murine-il-18-binding-protein-antibodies-to-stimulate-il-18-bioactivity\/"},"modified":"2025-02-28T12:59:36","modified_gmt":"2025-02-28T11:59:36","slug":"development-of-anti-murine-il-18-binding-protein-antibodies-to-stimulate-il-18-bioactivity","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/02\/28\/development-of-anti-murine-il-18-binding-protein-antibodies-to-stimulate-il-18-bioactivity\/","title":{"rendered":"Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jan 1;214(1):180-191. doi: 10.1093\/jimmun\/vkae022. Epub 2025 Jan 28.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Interleukin (IL)-18 is an immunoregulatory cytokine that acts as a potent inducer of T helper 1 and cytotoxic responses. IL-18 activity is regulated by its decoy receptor IL-18 binding protein (IL-18BP) which forms a high affinity complex with IL-18 to block binding of the cognate receptors. A disbalance between IL-18 and IL-18BP associated with excessive IL-18 signaling can lead to systemic inflammation. Indeed, the severity of CpG-induced macrophage activation syndrome (MAS) is exacerbated in IL-18BP KO mice. On the contrary, targeting IL-18BP can have promising effects to enhance immune responses against pathogens and cancer. We generated monoclonal rabbit anti-mouse IL-18BP antibodies labeled from 441 to 450. All antibodies, except from antibody 443, captured mIL-18BP when used in a sandwich ELISA. Using an IL-18 bioassay, we showed that antibody 441 did not interfere with the regulatory effect of mIL-18BP, whereas all other antibodies displayed different levels of antagonism. Further experiments were performed using antibody 445 endowed with potent neutralizing activity and antibody 441. Despite binding to IL-18BP with the same affinity, antibody 445, but not antibody 441, was able to release IL-18 from preformed IL-18-IL-18BP complexes. Administration of antibody 445 significantly aggravated the severity of CpG-induced MAS as compared to antibody 441. Additional experiments using na\u00efve WT, IL-18BP KO, and IL-18 KO mice confirmed the specificity of the neutralizing effect of antibody 445 towards IL-18BP. Our studies led to the development of a monoclonal anti-IL-18BP antibody with neutralizing activity that results in the promotion of IL-18 activities.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40018678\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250228065934&amp;v=2.18.0.post9+e462414\">40018678<\/a> | PMC:<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/PMC7617445\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250228065934&amp;v=2.18.0.post9+e462414\">PMC7617445<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkae022\">10.1093\/jimmun\/vkae022<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jan 1;214(1):180-191. doi: 10.1093\/jimmun\/vkae022. Epub 2025 Jan 28. ABSTRACT Interleukin (IL)-18 is an immunoregulatory cytokine that acts as a potent inducer of T helper 1 and cytotoxic responses. IL-18 activity is regulated by its decoy receptor IL-18 binding protein (IL-18BP) which forms a high affinity complex with IL-18 to block binding of &#8230; <a title=\"Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/02\/28\/development-of-anti-murine-il-18-binding-protein-antibodies-to-stimulate-il-18-bioactivity\/\" aria-label=\"Read more about Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-25851","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/25851","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=25851"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/25851\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=25851"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=25851"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=25851"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}