The role of IL-4 and IL-10 cytokines in controlling an anti-tumor response in vivo

The effect of systemic administration of anti-inflammatory cytokines (IL-4and IL-10) on the development and maintenance of an anti-tumor rejectionresponse in vivo was studied by following the growth patterns of P815.B7tumors on B6D2F1 [(C57BI/6 x DBA/2)F1] mice. The anti- P815.B7 rejectionresponse was found to be T cell dependent, involving both CD4 and CD8cells. IL-4 treatment resulted in a compromised rejection response; IL-10treatment alone had little or no effect. These results demonstrate thattreatment with an anti-inflammatory cytokine can compromise an otherwiseeffective anti-tumor rejection response. For the anti-inflammatory cytokineIL-4, the immunosuppressive effects of the cytokine appear to outweigh anypossible anti-tumor activities as have been reported using tumor cellsgenetically altered to produce IL-4. Relatively high systemic doses ofIL-10, in contrast, were not immunosuppressive and, when given incombination with IL-4, countered the IL-4 suppressive effect.Pathologically, IL-4 treatment led to splenomegaly characterized by amarked increase in neutrophils and NK activity. The possible linkagesbetween neutrophils, NK activity and IL-12 are discussed.