Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis

We have used interleukin (IL)-4 and -10-producing HSV-1 gamma (1)34.5 delet ion viruses in gene therapy of a BALB/c model of experimental allergic ence phalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous system, it is known that in EAE of mice the Th2-type cytokines are down-regulated and the Th1-type cytokines up-regulated during the onset an d relapse of the disease. Therefore, we tested two HSV-1 recombinants expre ssing the Th2-type cytokines IL-4 and IL-10. The recombinant viruses were i njected intracranially (i.c.) in BALB/c mice 6 days after induction of EAE. As control groups we used mice without any infection, mice infected with b ackbone virus R3659 and mock-infected mice. Weights and symptoms of the mic e were recorded daily and the tissue specimens were collected at specific t ime-points. The results indicate that the intracranial infection with IL-4- producing virus (1) precludes EAE symptoms, (2) protects the spinal cord fr om massive leukocyte infiltrations and (3) prevents demyelination and axona l loss. The IL-10-expressing virus R8308 did not have a similar favorable e ffect on the recovery of the mice as did the IL-4 virus R8306.