The role of tumour-derived mIL-4 on rat C6 glioma regression: A paradox between tumour volume and tumour pathology

Interleukin-4 (IL-4) has been demonstrated to possess anti-tumourigenic properties in vivo which is attributed to the infiltration of eosinophils in addition to an inhibition of tumour vascularisation. We have previously generated stable transfectants of C6 glioma cells that express mouse IL-4 (mIL-4) under a tetracycline-responsive promoter system, enabling us to apply tight regulatory control of mIL-4 expression in vivo. We have demonstrated that the subcutaneous implantation of mIL-4 expressing rat C6 glioma cell lines in nu/nu mice resulted in an inhibition of tumour growth. In this study, we have investigated the ability of mIL-4 to potentiate the regression of established subcutaneous rat C6 tumours in nu/nu mice. Induction of mIL-4 re-expression in established tumours did not cause a regression of tumour growth as determined by external tumour volume measurements. However, histological analysis revealed that mIL-4 re-expressing tumours were highly necrotic, were infiltrated by eosinophils and had a reduced level of vascularisation. These results suggest that mIL-4 can potentiate an anti-tumourigenic response in established C6 tumours in nu/nu mice. Furthermore, this study illustrates the need for detailed and defined tumour histopathology as tumour volume measurements alone can lead to inaccurate and misleading results.