Object: The aim of this study was to investigate the association of interleukin-1beta (IL-1beta) expression with improved survival in patients with glioblastomas multiforme (GBMs). Immune and vascular host-tumor interactions play a pivotal role in the control of tumor development, and inflammatory mechanisms may participate in the host's defense against tumor cells. Expression of proinflammatory cytokines and of inducible nitric oxide synthase (iNOS) has been noted in various types of malignant tumors, raising the possibility that endogenous expression of cytokines and the resulting cytotoxic action of sustained NO production play a role in the control of tumor growth. Indeed, human GBMs express variable amounts of iNOS.
Methods: In this study, the expression of iNOS and of cytokines known to upregulate IL-1beta, tumor necrosis factor-alpha, interferon-gamma or downregulate iNOS transcription (IL-10, transforming growth factor [TGF]beta1, and TGFbeta2) were measured using reverse transcription-polymerase chain reaction with competitor DNA in 39 samples of human GBM. The iNOS level in GBM was positively correlated with IL-1beta messenger (m)RNA, but not with the other cytokines tested. Immunocytochemical double labeling revealed that both anti-iNOS immunoreactivity and anti-IL-1beta immunoreactivity colocalized with glial fibrillary acidic protein immunoreactivity in GBM. Some macrophage/microglial cells also expressed iNOS, but not IL-1beta. Comparison of biological data with clinical parameters indicated that the survival duration was enhanced when levels of IL-1beta mRNA were elevated or when levels of TGFbeta2 were low, but was independent of the level of iNOS mRNA within the tumor.
Conclusions: Taken together, these data indicate that the proinflammatory cytokine IL-1beta produced within GBM by glial-derived cells has a negative impact on tumor growth through a mechanism independent of iNOS induction.