Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma

Biotherapy including interleukin-2 (IL-2) treatment seems to be more effect ive outside the central nervous system when compared to the effects obtaine d when the same tumour is located intracerebrally. Recently published studi es suggest that reduced activity of NK cells in tumour tissue can be increa sed by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in a n orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1) s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcuta neous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density wa s significantly reduced, an effect mainly affecting the small vessels. No o bvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malig nant glioma. (C) 2000 Cancer Research Campaign.