{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huard A"],"funding":["Swiss National Science Foundation"],"pagination":["180-191"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617445"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["214(1)"],"pubmed_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 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 naïve 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."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity."],"pmcid":["PMC7617445"],"funding_grant_id":["201269"],"pubmed_authors":["Gabay C","Diaz-Barreiro A","Savvides SN","Huard A","Caruso A","Andries J","Martin P","Vaillant L","Fauteux-Daniel S","Goldstein J","Rodriguez E","Jarlborg M"],"additional_accession":[]},"is_claimable":false,"name":"Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity.","description":"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 naïve 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-03T01:23:54.765Z","creation":"2025-04-04T02:05:06.773Z"},"accession":"S-EPMC7617445","cross_references":{"pubmed":["40018678"],"doi":["10.1093/jimmun/vkae022"]}}