Cytokine patterns in brain tumour progression

Abstract

Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body's response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β , IL-6, IL-8, IL-12, GM-CSF, and TNF-α ) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β , TNF-α , and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in a generation of disease associated pain.

Figure 1

Implication of chronic inflammation in different stages of tumour development. Mediators of inflammation, triggered by different processes, may stimulate premalignant cell proliferation, angiogenesis, and metastasis. Reversely, tumour cells have the ability to stimulate other cells or to produce by themselves pro inflammatory and pro-angiogenic factors.

Figure 2

Modulation of serum cytokine levels in glioblastoma patients. The data represent group averages of fold modification versus controls + standard deviations. Statistical significance (one way ANOVA): pro-inflammatory cytokines, P < 0.05 for IL-1β, IL-6, and TNFα, GM-CSF; anti-inflammatory cytokines, P < 0.05 for IL-4, and IL-10; angiogenic factors, P < 0.05 for bFGF and VEGF. Expression levels of IL-2, IL-8, IFN-γ, and IL-12 were modified, but with low statistical significance.

Figure 3

Serum levels of pro-inflammatory cytokines xMAP analysis. Statistical significance (one way Anova): P < 0.05 for over-expression of IL-1β, TNFα, IL-6, and GM-CSF in sera from glioblastoma patients compared to control.

Figure 4

Expression levels of anti-inflammatory cytokines by xMAP analysis. Statistical significance (one way Anova): P < 0.05 for IL-4 and IL-10 modified levels in patients' sera versus controls.

Figure 5

Expression levels of angiogenic factors, by xMAP analysis (a and b) and ELISA (c and d). Statistical significance (one way Anova): P < 0.05 for bFGF and VEGF over-expression in sera from glioblastoma patients versus control, by both methods.