Abstract:
:The proinflammatory cytokine IL-18 mediates IFN-gamma production as well as the induction of Th1 polarized immune responses in synergy with IL-12. In this study, we describe the production of isogeneic monoclonal antibodies (Mabs) directed against murine IL-18 (mIL-18). Immunization of IL-18-deficient mice with recombinant mIL-18 in the presence of CpG-oligodeoxynucleotides (CpG-ODN) and alum as adjuvant resulted in high anti-IL-18 serum titers. We could identify two Mabs, SK721-2 and SK113AE-4, which were able to bind to IL-18 and neutralize its IFN-gamma inducing effect in vitro with an IC(50) of 40-100 ng/ml. In vivo, LPS-induced IFN-gamma production was reduced by 60-85% following a single administration of Mabs SK113AE-4 or SK721-2. Since IL-18 is likely to be involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis or Crohn's disease, neutralizing mouse anti-mouse IL-18 Mabs have the potential to become valuable tools for the therapeutic exploration of long-term IL-18 blockade in vivo.
journal_name
J Immunol Methodsjournal_title
Journal of immunological methodsauthors
Lochner M,Wagner H,Classen M,Förster Idoi
10.1016/s0022-1759(01)00505-1keywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
149-57issue
1-2eissn
0022-1759issn
1872-7905pii
S0022175901005051journal_volume
259pub_type
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