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-4 and IL-10) on the development and maintenance of an anti-tumor rejection response in vivo was studied by following the growth patterns of P815.B7 tumors on B6D2F1 [(C57BI/6 x DBA/2)F1] mice. The anti-P815.B7 rejection response was found to be T cell dependent, involving both CD4 and CD8 cells. IL-4 treatment resulted in a compromised rejection response; IL-10 treatment alone had little or no effect. These results demonstrate that treatment with an anti-inflammatory cytokine can compromise an otherwise effective anti-tumor rejection response. For the anti-inflammatory cytokine IL-4, the immunosuppressive effects of the cytokine appear to outweigh any possible anti-tumor activities as have been reported using tumor cells genetically altered to produce IL-4. Relatively high systemic doses of IL-10, in contrast, were not immunosuppressive and, when given in combination with IL-4, countered the IL-4 suppressive effect. Pathologically, IL-4 treatment led to splenomegaly characterized by a marked increase in neutrophils and NK activity. The possible linkages between neutrophils, NK activity and IL-12 are discussed.
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94304, USA.
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D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen; D013491:Suppressor Factors, Immunologic; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; D016753:Interleukin-10; D015847:Interleukin-4