THE ROLE OF IL-4 AND IL-10 CYTOKINES IN CONTROLLING AN ANTITUMOR RESPONSE IN-VIVO

The effect of systemic administration of anti-inflammatory cytokines ( IL-4 and IL-10) on the development and maintenance of an anti-tumor re jection response in vivo was studied by following the growth patterns of P815.B7 tumors on B6D2F1 [(C57BI/6 x DBA/2)F-1] mice. The anti-P815 .B7 rejection response was found to be T cell dependent, involving bot h CD4 and CD8 cells. IL-4 treatment resulted in a compromised rejectio n response; IL-10 treatment alone had little or no effect. These resul ts demonstrate that treatment with an anti-inflammatory cytokine can c ompromise an otherwise effective anti-tumor rejection response. For th e anti-inflammatory cytokine IL-4, the immunosuppressive effects of th e cytokine appear to outweigh any possible antitumor activities as hav e been reported using tumor cells genetically altered to produce IL-4. Relatively high systemic doses of IL-10, in contrast, were not immuno suppressive and, when given in combination with IL-4, countered the IL -4 suppressive effect. Pathologically, IL-4 treatment led to splenomeg aly characterized by a marked increase in neutrophils and NK activity. The possible linkages between neutrophils, NK activity and IL-12 are discussed.