Format

Send to

Choose Destination
J Neurooncol. 2017 Jan;131(1):83-92. doi: 10.1007/s11060-016-2271-1. Epub 2016 Sep 23.

Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study.

Author information

1
Department of Clinical Neuroscience, Neurosurgery, Umea University, 901 85, Umeå, Sweden. pedram.tabatabaie@vll.se.
2
Department of Clinical Science, Lund University Hospital, 221 85, Lund, Sweden.
3
Department of Radiation Science, Umeå University, 901 85, Umeå, Sweden.
4
Department of Medical Bioscience, Umeå University, 901 85, Umeå, Sweden.
5
Department of Clinical Neuroscience, Neurosurgery, Umea University, 901 85, Umeå, Sweden.

Abstract

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.

KEYWORDS:

Cytokine; Glioblastoma; Inflammation; Microdialysis; Radiotherapy

PMID:
27664151
PMCID:
PMC5258803
DOI:
10.1007/s11060-016-2271-1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center