CENTRAL-NERVOUS-SYSTEM CYTOKINE MESSENGER-RNA EXPRESSION FOLLOWING THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INFECTION

DA strain of Theiler's murine encephalomyelitis virus (TMEV) produces a biphasic disease with an initial self-limited acute gray matter poli oencephalomyelitis in all strains of mice followed by, in the case of certain susceptible strains of mice, a chronic inflammatory demyelinat ion of the spinal cord with a persistent virus infection. A pathogenic role for T-helper 1 (Th1) cells during the demyelinating phase of dis ease has been proposed. We characterized the cytokine mRNA expression in the brain and spinal cord of susceptible and resistant strains of m ice during the early encephalomyelitic disease and the late demyelinat ion, using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. At the time of the encephalomyelitis, both re sistant and susceptible mice expressed proinflammatory cytokine mRNAs followed by T-cell derived mRNAs; susceptible mice expressed more IL-1 2 p40 mRNA than resistant mice. During this early disease, there was n o significant difference in Th1 cytokine mRNA expression in the brain and spinal cord among the four strains and relatively little Th2 type cytokine upregulation above levels seen in mock-infected controls. Dur ing the late demyelinating disease, susceptible but not resistant mice had evidence of viral genome and a continuous expression of Th1 type cytokine mRNAs. The expression of Th2 cytokine mRNAs varied among the different strains and did not correlate with susceptibility or resista nce. The results indicate the complexity of cytokine mRNA expression f ollowing TMEV infection and the dependence of the expression on diseas e pathology, the time following infection and the genetics of the host .