Generation of neutralizing mouse anti-mouse IL-18 antibodies for inhibition of inflammatory responses in vivo.
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.
Lochner
Matthias
M
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Wagner
Hermann
H
Classen
Meinhard
M
Förster
Irmgard
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use; D005260:Female; D007167:Immunotherapy; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; C408982:CPG-oligonucleotide; D020382:Interleukin-18; D007519:Isoantigens; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; C041524:aluminum sulfate; D007371:Interferon-gamma