DEFECTIVE EXPRESSION OF INTERFERON-GAMMA, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERLEUKIN-6 IN ACTIVATED PERIPHERAL-BLOOD LYMPHOCYTES FROM GLIOMA PATIENTS

The ability of a mannoprotein antigen from Candida albicans (MP) or in terleukin-2 (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression and by protein secretion. The subjects st udied were all responsive to both MP and IL-2, as assayed by lymphopro liferation of PBMC cultures. In control subjects, MP and IL-2 were str ong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expre ssion, but only MP was able to induce considerable levels of IL-6 and IL-2 mRNA expression. In MP-activated PBMC from glioma subjects, a hig hly defective IFN-gamma, together with a significant reduction in TNF- gamma and GM-CSF mRNA expression, was observed. This impairment was pa ralleled by a decreased accumulation of IL-6 and IL-2 mRNA. The patter n of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirme d the impairment of IFN-gamma mRNA expression paralleled by a reductio n in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects. Coherently, in PBMC cultures from glioma patients, there was a clear-c ut decrease in the secretion of IL-6 and TNF-alpha and especially of I FN-gamma compared with healthy controls. No or very low levels of IL-4 , IL-10, and TGF-beta(2) mRNA expression were detected in PBMC culture s of both glioma and control populations, irrespective of the activati on conditions. Considering the cytokine network and the key, pivotal r ole played by IFN-gamma in the activation of antitumor cytotoxicity, w e suggest that a defective IFN-gamma production can be a key immunolog ic defect in glioma patients.