Use of recombinant viruses to deliver cytokines influencing the course of experimental bacterial infection

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.