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Interleukin 4 Retards Dissemination of a Human B-Cell Lymphoma in Severe Combined Immunodeficient Mice

Immunology Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

We have examined the antitumor activity of murine interleukin 4 (IL-4) on development of a human B-cell lymphoma (Daudi) in severe combined immunodeficient (SCID) mice. The progression of Daudi cells in SCID mice was followed by histological staining and by flow cytometric analysis of CD20⁺ cells in spleen, liver, bone marrow, and kidneys. By day 35, CD20⁺ Daudi cells populate the majority of space in the bone marrow and kidney in vehicle-treated mice. Mice receiving i.p. injections of IL-4, commencing 7 or 14 days after tumor inoculation, exhibit a reduction in tumor burden as well as a decrease in CD20⁺ cells in both compartments. The antitumor activity of IL-4 does not appear to be due to an antiproliferative effect, since the cytokine does not alter the growth of Daudi cells in vitro, nor does it correlate with any marked cellular infiltrate in tumor-bearing tissues. In ⁵¹Cr-release assays, we observed that splenocytes from IL-4-treated mice were capable of lysing YAC-1 but not Daudi cell targets. Our findings demonstrate that: (a) systemic administration of IL-4 retards dissemination of a human B-cell lymphoma in SCID mice; and (b) antitumor activity elicited by IL-4 may not involve a direct effect on proliferation of Daudi cells or on the induction of cytolytic activity.

¹ To whom requests for reprints should be addressed, at Immunology Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033.

Received 6/19/95. Accepted 7/24/95.

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