The present study was aimed at investigating whether the expression of Fas
ligand (FasL) by CHO cells transfected with IL-4 (CHO/IL-4) or IL-10 (CHO/I
L-10) genes would improve the effect of the cytokine. DBA/1 mice immunized
with type II collagen were treated with suboptimal doses of transfected CHO
cells (a single s. c. injection of 2 x 10(5) cells) around onset of arthri
tis. Severe collagen-induced arthritis (CIA) developed in the control group
s injected with PBS, CHO/beta-galactosidase/FasL, CHO/IL-4 or CHO/IL-10 cel
ls. In contrast, administration of CHO/IL-4/FasL, but not CHO/IL-10/FasL, c
ells significantly reduced the clinical severity and resulted in rapid and
sustained suppressive effect, Amelioration of CIA was not due to a prolonge
d in vivo secretion of IL-4 since expression of Fast by CHO cells shortened
the in vivo survival of the xenogeneic cells. In fact, administration of F
asL(+) cells was associated with a decreased proportion of Mac1(+) neutroph
ils in the blood and an increased expression of myeloperoxidase at the site
of engineered cell engraftment. These findings suggest that the mechanism
underlying the beneficial effect of IL-4 delivered by cells expressing Fast
involves the combination of the anti-inflammatory properties of IL-4 and t
he apoptosis of Fas(+) Mac1(+) granulocytes participating in the pathogenic
process.