Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study.
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.
Department of Clinical Neuroscience, Neurosurgery, Umea University, 901 85, Umeå, Sweden. pedram.tabatabaie@vll.se.
Pedram
0000-0003-2912-7059
P
Tabatabaei
Department of Clinical Science, Lund University Hospital, 221 85, Lund, Sweden.
Eward
E
Visse
Department of Radiation Science, Umeå University, 901 85, Umeå, Sweden.
Per
P
Bergström
Department of Medical Bioscience, Umeå University, 901 85, Umeå, Sweden.
Thomas
T
Brännström
Department of Clinical Science, Lund University Hospital, 221 85, Lund, Sweden.
Peter
P
Siesjö
Department of Clinical Neuroscience, Neurosurgery, Umea University, 901 85, Umeå, Sweden.
A Tommy
AT
Bergenheim
D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005990:Glycerol; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*; D018709:Statistics, Nonparametric
D016207:Cytokines; D018698:Glutamic Acid; D005947:Glucose; D005990:Glycerol
Cytokine; Glioblastoma; Inflammation; Microdialysis; Radiotherapy
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