The Journal of Immunology, Vol 155, Issue 12 5684-5689, Copyright © 1995 by American Association of Immunologists

ARTICLES

IL-12 promotes enhanced recovery from vesicular stomatitis virus infection of the central nervous system

Z Bi, P Quandt, T Komatsu, M Barna and CS Reiss
Department of Biology, Kaplan Comprehensive Cancer Center, New York University, New York 10003, USA.

To investigate the role of a cytokine in host defense against the vesicular stomatitis virus (VSV) infection of the central nervous system (CNS), IL-12 was injected i.p. into groups of 10 BALB/c mice on days -1, 0, 1, 2, and 3 postinfection. Four days postinfection, mice were examined. IL-12 strongly enhanced immunity to VSV infection in the CNS as demonstrated by 1) decreased VSV titers in brain homogenate of IL-12-injected mice compared with those of controls; 2) increased expression of inducible nitric oxide synthase in the CNS; 3) enhanced expression of both MHC class I and class II Ags in the CNS; 4) increased T cell infiltration in the CNS, especially in the olfactory bulb; and 5) diminished VSV-induced apoptosis in olfactory bulb. No detrimental effect was observed even with the 200 ng/mouse dose of IL- 12. Protective effects of IL-12 were dose dependent. Collectively, these results demonstrate that exogenously added IL-12, even when injected peripherally, significantly enhances recovery from VSV infection of the CNS.

This article has been cited by other articles:

				C. Trudeau, M. M. Cotreau, L. Stonis, K. H. Dykstra, J. L. Oestreicher, A. Strahs, A. J. Dorner, V. H. Van Cleave, W. L. Trepicchio, and U. S. Schwertschlag A Single Administration of Recombinant Human Interleukin-12 Is Associated With Increased Expression Levels of Interferon-gamma and Signal Transducer and Activator of Transcription in Healthy Subjects J. Clin. Pharmacol., June 1, 2005; 45(6): 649 - 658. [Abstract] [Full Text] [PDF]

				E. L. Oleszak, J. R. Chang, H. Friedman, C. D. Katsetos, and C. D. Platsoucas Theiler's Virus Infection: a Model for Multiple Sclerosis Clin. Microbiol. Rev., January 1, 2004; 17(1): 174 - 207. [Abstract] [Full Text] [PDF]

				A. Smith, F. Santoro, G. Di Lullo, L. Dagna, A. Verani, and P. Lusso Selective suppression of IL-12 production by human herpesvirus 6 Blood, October 15, 2003; 102(8): 2877 - 2884. [Abstract] [Full Text] [PDF]

				J.-H. Sur, R. Allende, and A. R. Doster Vesicular Stomatitis Virus Infection and Neuropathogenesis in the Murine Model are Associated with Apoptosis Vet. Pathol., September 1, 2003; 40(5): 512 - 520. [Abstract] [Full Text] [PDF]

				E. B. Flanagan, T. R. Schoeb, and G. W. Wertz Vesicular Stomatitis Viruses with Rearranged Genomes Have Altered Invasiveness and Neuropathogenesis in Mice J. Virol., May 15, 2003; 77(10): 5740 - 5748. [Abstract] [Full Text] [PDF]

				K. J. Maloy, C. Burkhart, T. M. Junt, B. Odermatt, A. Oxenius, L. Piali, R. M. Zinkernagel, and H. Hengartner CD4+ T Cell Subsets during Virus Infection: Protective Capacity Depends on Effector Cytokine Secretion and on Migratory Capability J. Exp. Med., June 19, 2000; 191(12): 2159 - 2170. [Abstract] [Full Text] [PDF]

				G. C. Pien and C. A. Biron Compartmental Differences in NK Cell Responsiveness to IL-12 During Lymphocytic Choriomeningitis Virus Infection J. Immunol., January 15, 2000; 164(2): 994 - 1001. [Abstract] [Full Text] [PDF]

				M. van den Broek, M. F. Bachmann, G. Kohler, M. Barner, R. Escher, R. Zinkernagel, and M. Kopf IL-4 and IL-10 Antagonize IL-12-Mediated Protection Against Acute Vaccinia Virus Infection with a Limited Role of IFN-{gamma} and Nitric Oxide Synthetase 2 J. Immunol., January 1, 2000; 164(1): 371 - 378. [Abstract] [Full Text] [PDF]

				J.-I. Sin, J. J. Kim, R. L. Arnold, K. E. Shroff, D. McCallus, C. Pachuk, S. P. McElhiney, M. W. Wolf, S. J. Pompa-de Bruin, T. J. Higgins, et al. IL-12 Gene as a DNA Vaccine Adjuvant in a Herpes Mouse Model: IL-12 Enhances Th1-Type CD4+ T Cell-Mediated Protective Immunity Against Herpes Simplex Virus-2 Challenge J. Immunol., March 1, 1999; 162(5): 2912 - 2921. [Abstract] [Full Text] [PDF]

				F. Aloisi, G. Penna, E. Polazzi, L. Minghetti, and L. Adorini CD40-CD154 Interaction and IFN-{gamma} Are Required for IL-12 But Not Prostaglandin E2 Secretion by Microglia During Antigen Presentation to Th1 Cells J. Immunol., February 1, 1999; 162(3): 1384 - 1391. [Abstract] [Full Text] [PDF]

				J. M. Monteiro, C. Harvey, and G. Trinchieri Role of Interleukin-12 in Primary Influenza Virus Infection J. Virol., June 1, 1998; 72(6): 4825 - 4831. [Abstract] [Full Text] [PDF]

				A. Fernandez-Sesma, R. W. Peluso, X. Bai, J. L. Schulman, D. E. Levy, and T. M. Moran Superantigen-Activated T Cells Redirected by a Bispecific Antibody Inhibit Vesicular Stomatitis Virus Replication In Vitro and In Vivo J. Immunol., February 15, 1998; 160(4): 1841 - 1849. [Abstract] [Full Text] [PDF]