C. Cheers et al., Use of recombinant viruses to deliver cytokines influencing the course of experimental bacterial infection, IMM CELL B, 77(4), 1999, pp. 324-330
The feasibility of using viral constructs expressing cytokine genes to infl
uence the course of bacterial infection was tested in mice. The mice were f
irst infected with vaccinia or fowlpox viruses expressing the cytokine of i
nterest, then challenged with the facultative intracellular bacterial patho
gen Listeria monocytogenes. The course of infection was assessed by subsequ
ent bacterial counts. Expression of IFN-gamma or TNF was protective. Vaccin
ia virus was more efficient at delivering IFN-gamma-mediated protection tha
n was fowlpox virus, which is unable to proliferate in mammalian cells. The
effect of vaccinia-IFN-gamma was more apparent in the liver, where vaccini
a proliferates to high titres (> 10(9)), than in the spleen, where only 10(
3) vaccinia were isolated. Vaccinia virus expressing IL-4 exacerbated infec
tion. Interleukin-4 exacerbation was T cell independent and was reflected i
n the failure of macrophage activation, possibly due to suppression of NK c
ells, which are a source of IFN-gamma early in infection. The clear indicat
ion of protection by some cytokines in this prophylactic model appears to j
ustify further study of the therapeutic effects of cytokine-expressing viru
ses in chronic bacterial infections, especially where a cytokine defect is
suspected.