The role of interleukin-18 in vesicular stomatitis virus infection of the CNS.
Intranasal application of vesicular stomatitis virus (VSV) results in the initial infection of the olfactory receptor neurons and a rapid progression of the virus through the mouse central nervous system (CNS). Interleukin-18 (IL-18) is an 18.3-kd cytokine that induces interferon gamma (IFN-gamma) production in mice. IL-18 is synthesized as an inactive precursor that is cleaved and activated by caspase-1/interleukin-1beta converting enzyme (ICE). IL-18 shares several biological properties with IL-12, including the ability to induce IFN-gamma production in T lymphocytes and natural killer (NK) cells. In the CNS, microglia and astrocytes produce IL-18 and IL-12. We have previously shown that IL-12 promotes recovery from VSV encephalitis. This led us to examine the potential role of IL-18 in the pathogenesis of VSV encephalitis. We show that both IL-18 and caspase-1 mRNA are consistently present in the CNS of mice. The addition of exogenous IL-18 to cell cultures does not affect the production of VSV, and addition of exogenous IL-18 at the time of infection does not alter the morbidity or mortality of BALB/c mice. In vitro studies with neutralizing monoclonal antibody to IL-18 had no effect. From these results we conclude that in this system and under the experimental conditions used, unlike IL-12 and IFN-gamma, IL-18 does not play a significant role in the host response to VSV infection.
Hodges
J L
JL
Department of Biology, New York University, New York 10003-6688, USA.
Ireland
D D
DD
Reiss
C S
CS
D000818:Animals; D020170:Caspase 1 / Q000235:genetics; D020805:Central Nervous System Viral Diseases / Q000209:etiology*; D015151:Immunoblotting; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000821:virology; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018353:Rhabdoviridae Infections / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000302:isolation & purification
D020382:Interleukin-18; D012333:RNA, Messenger; D009569:Nitric Oxide; D020170:Caspase 1