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 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (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 and relapse of the disease. Therefore, we tested two HSV-1 recombinants expressing the Th2-type cytokines IL-4 and IL-10. The recombinant viruses were injected 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 backbone virus R3659 and mock-infected mice. Weights and symptoms of the mice were recorded daily and the tissue specimens were collected at specific time-points. The results indicate that the intracranial infection with IL-4-producing virus (1) precludes EAE symptoms, (2) protects the spinal cord from massive leukocyte infiltrations and (3) prevents demyelination and axonal loss. The IL-10-expressing virus R8308 did not have a similar favorable effect on the recovery of the mice as did the IL-4 virus R8306.
Broberg
E
E
Department of Virology, University of Turku, Turku, Finland.
Setälä
N
N
Röyttä
M
M
Salmi
A
A
Erälinna
J P
JP
He
B
B
Roizman
B
B
Hukkanen
V
V
D000818:Animals; D001921:Brain / Q000821:virology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D013116:Spinal Cord / Q000821:virology; D018709:Statistics, Nonparametric
D016753:Interleukin-10; D015847:Interleukin-4