E. Raz et al., SYSTEMIC IMMUNOLOGICAL EFFECTS OF CYTOKINE GENES INJECTED INTO SKELETAL-MUSCLE, Proceedings of the National Academy of Sciences of the United Statesof America, 90(10), 1993, pp. 4523-4527
Somatic gene therapy is an interesting approach for the delivery of cy
tokines for prolonged periods. The present experiments show that direc
t injections into mouse skeletal muscle of cDNA expression vectors enc
oding interleukin 2 (IL-2), IL-4, or type beta1 transforming growth fa
ctor (TGF-beta1) induce biological effects characteristic of these cyt
okines in vivo. Mice injected intramuscularly with a vector encoding I
L-2 had enhanced humoral and cellular immune responses to an exogenous
antigen, transferrin, that was delivered at a separate site. These IL
-2 effects were abolished by coadministration of a vector directing sy
nthesis of TGF-beta1. The TGF-beta1 vector by itself depressed the ant
i-transferrin antibody response and caused an 8-fold increase in plasm
a TGF-beta1 activity. The TGF-beta1 plasmid injection did not cause mu
scle infiltration with monocytes or neutrophils and there was no evide
nce for fibrotic changes. Muscle injection with a cDNA encoding IL-4 s
electively increased IgG1 levels but did not alter the cellular immune
response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection
with IL-2 expression vectors increased and TGF-beta1 vectors decrease
d autoantibodies to chromatin. These results demonstrate that intramus
cular injection of cytokine genes, in the absence of infectious viral
vectors, can regulate humoral and cellular immune responses in vivo.