Enhanced cytokines delivery and intercellular adhesion molecule 1 (ICAM-1) expression in glioma by intracarotid infusion of bradykinin analog, RMP-7.
The effect of intracarotid infusion of the bradykinin analog, RMP-7, on blood-to-tumor and blood-to-brain transport of three cytokines were investigated. Wistar rats with RG2 gliomas were utilized and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) were labeled with 125Iodine for quantitative transport studies using autoradiography. Radiolabeled cytokines were injected as an intravenous bolus. Intracarotid infusion of RMP-7 (0.1 microgram kg-1 min-1) increased the selective transport to tumors of IFN-gamma by 3.97-fold (p < 0.005), of TNF-alpha by 5.30-fold (p < 0.005), and of IL-2 by 4.34-fold (p < 0.005), compared to intracarotid saline infusion. To determine whether the increased IFN-gamma or TNF-alpha transport to tumors with RMP-7 could enhance expression of intercellular adhesion molecule 1 (ICAM-1) in tumors, ICAM-1 expression in RG2 glioma was evaluated by immunohistochemistry. Both IFN-gamma and TNF-alpha increased ICAM-1 expression of RG2 cells in vitro. In vivo, intracarotid infusion of IFN-gamma combined with RMP-7 significantly enhanced ICAM-1 expression in intracerebral RG2 gliomas compared to infusion of IFN-gamma without RMP-7. Expression of ICAM-1 was not enhanced by TNF-alpha combined with RMP-7. Intracarotid infusion of RMP-7 is a novel method of cytokines delivery to brain tumors.
Nakano
S
S
Jonsson Comprehensive Cancer Center, Division of Neurosurgery, UCLA Medical Center 90095, USA.
Matsukado
K
K
Black
K L
KL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability; D016207:Cytokines / Q000493:pharmacokinetics*; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D007261:Infusions, Intra-Arterial; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000493:pharmacokinetics; D007376:Interleukin-2 / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics
D016207:Cytokines; D007376:Interleukin-2; D007457:Iodine Radioisotopes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C089876:RMP 7; D007371:Interferon-gamma; D001920:Bradykinin