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 interleukin-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 studied were all responsive to both MP and IL-2, as assayed by lymphoproliferation of PBMC cultures. In control subjects, MP and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expression, 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 highly defective IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA expression, was observed. This impairment was paralleled by a decreased accumulation of IL-6 and IL-2 mRNA. The pattern of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects. Coherently, in PBMC cultures from glioma patients, there was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of IFN-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 cultures of both glioma and control populations, irrespective of the activation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Urbani
F
F
Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy.
Maleci
A
A
La Sala
A
A
Lande
R
R
Ausiello
C M
CM
D001254:Astrocytoma / Q000188:drug therapy / Q000235:genetics; D001623:Betamethasone / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C025363:mannoproteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001623:Betamethasone