MODULATION OF PROLIFERATION AND ANTIGEN EXPRESSION OF A CLONED HUMAN GLIOBLASTOMA BY INTERLEUKIN-4 ALONE AND IN COMBINATION WITH TUMOR-NECROSIS-FACTOR-ALPHA AND OR INTERFERON-GAMMA

AS PART OF continuing studies to investigate the possible regulatory e ffects of cytokines on malignant astrocytes, we investigated the effec ts of interleukin-4 (IL-4) alone and in combination with tumor necrosi s factor-alpha (TNFalpha) and/or interferon-gamma (IFNgamma) on the ce ll growth and major histocompatibility complex (MHC) antigen expressio n of a cloned human glioblastoma cell line (9C). The 9C cells were tre ated with IL-4 alone or in combination with TNFalpha and/or IFNgamma a nd were examined for proliferation by crystal violet assay and for Cla ss II MHC antigen by flow cytometry. Results indicated that IL-4 alone did not affect 9C proliferation. In combination with TNFalpha or IFNg amma, however, IL-4 significantly and dose-dependently inhibited cell growth. As previous reports have shown, TNFalpha combined with IFNgamm a exerted an additive growth suppressive effect on glioblastoma cells, probably by enhancing TNF receptor expression. This additive effect o f TNFalpha and IFNgamma was further enhanced by IL-4. In contrast, IL- 4 did not modulate expression of Class II MHC antigen on 9C cells, eve n in combination with IFNgamma, which predictably enhanced this antige n. These results suggest that IL-4 is capable of modulating glioblasto ma growth only in the presence of other cytokines, such as TNFalpha an d/or IFNgamma. Further, the effect of IL-4 on glioblastoma proliferati on is selective and independent of the mechanisms involved in regulati ng MHC antigen expression.