Inhibition of monocyte function in patients with glioblastomas

Introduction: Recent advances in immunology have emphasized the long-standing view that monocytes/macrophages play a critical role in the immune system. On the other hand it is known that patients with glioblastomas have a systemic immunosuppression. Methods: In order to determine the function of monocytes in glioblastoma (n = 23) and astrocytoma (n = 20) patients we investigated the expression of human leucocyte antigen-DR (HLA-DR) on peripheral blood monocytes before and after surgery. Furthermore we measured the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-10 and interleukin-1 receptor antagonist (IL-1ra) in culture supernatants after stimulation of white blood cells (WBC) with lipopolysaccharide (LPS). Results: Our results demonstrate an inactivation of peripheral blood monocytes in glioblastoma patients with a decreased percentage of HLA-DR positive monocytes compared with astrocytoma patients (p < 0.0001). Moreover, we could show that HLA-DR positive monocytes fell significantly on the first day after surgery in both patient groups (p < 0.01). 8 days after surgery there was a recovery of the HLA-DR expression with normal levels in astrocytoma patients and an increased percentage of HLA-DR positive monocytes in glioblastoma patients when compared with the values on admission (p < 0.05). However, there was still a significant difference comparing the values of glioblastoma patients with the values of astrocytoma patients on day 8 after surgery (p < 0.01). The LPS induced production of TNF-α and IL-1 and IL-10 by WBC on admission was significantly lower in glioblastoma patients compared with astrocytoma patients (p < 0.01 for TNF-α, p < 0.05 for IL-1 and IL-10). The values in astrocytoma patients were not significantly different from normal controls. However, in the astrocytoma patients there was a significant decrease of the LPS induced TNF-α release 1 day after surgery (p < 0.05). On the other hand the IL-1ra release of WBC from glioblastoma patients was not significantly different from patients with astrocytomas and normal controls. To investigate the role TGF-β and IL-10 in monocytic deactivation we measured these cytokines in plasma of both patient groups on admission. However there were no detectable values of IL-10 or TGF-β in plasma. Conclusions: Our results suggest that patients with glioblastoma have beside an impaired function of blood lymphocytes an additional deficit in blood monocyte function with the effect of systemic immunosuppression.