IL-12 stimulates an antiviral type 1 cytokine response but lacks adjuvant activity in IFN-gamma-receptor-deficient mice.
Cytokines can be used as adjuvants to enhance and direct protective immune responses induced by vaccines. IL-12, a cytokine that favors the maturation of Th1-type cells and stimulates associated cell-mediated responses was evaluated as immunologic adjuvant for a viral vaccine in a mouse challenge model. When it was administered together with inactivated pseudorabies virus, a herpes simplex virus related alpha-herpesvirus, increased production of IFN-gamma by ex vivo-stimulated splenocytes was observed as well as augmented production of antiviral serum lgG2a. This was associated with increased protection against a lethal challenge infection. Infection of IfN-gamma-neutralizing Ab reduced the increased antiviral resistance in IL-12-treated mice. Also, in mice bearing an inactivated IFN-gamma-receptor gene IL-12 failed to stimulate protection against challenge and the synthesis of antiviral lgG2a. However, in these IFN-gamma-receptor knockout mice, increased antiviral lgG2b levels and enhanced IFN-gamma-secretion, with minimal IL-4 production, by ex vivo-stimulated splenocytes was observed. In wild-type mice administration of recombinant IFN-gamma but not IL-2 mimicked the immune-stimulating activity of IL-12; it is therefore likely that the IL-12 adjuvant activity is largely mediated by physiologic IFN-gamma.
Schijns
V E
VE
Department of Infectious Diseases and Immunology, Veterinary Faculty, Ultrecht University, The Netherlands.
Haagmans
B L
BL
Horzinek
M C
MC
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects*; D005260:Female; D011558:Herpesvirus 1, Suid / Q000187:drug effects* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017471:Receptors, Interferon / Q000172:deficiency*; D011994:Recombinant Proteins / Q000494:pharmacology; D000096743:Interferon gamma Receptor
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor