Intrathecal treatment of C6 glioma leptomeningeal metastasis in Wistar rats with interleukin-2.
The efficacy of intrathecal treatment of leptomeningeal metastasis (LM) with interleukin-2 (IL-2) was evaluated in an animal model using Wistar rats inoculated intracisternally with 10(7) C6 glioma cells. Prior to the in vivo experiments the antiproliferative effects of human IL-2, and of murine IFN-gamma and TNF-alpha which are cytokines induced by IL-2 were tested in a colony forming assay. Only IFN-gamma caused a dose-dependent inhibition of colony formation. Twelve animals were treated intracisternally with either 10(5) IU IL-2 or control medium on day 0, 2, and 5 after tumor cell inoculation. Both IL-2 treated and sham-treated animals developed LM with a symptom-free survival of 7 to 9 days. There was no significant difference between treated and untreated animals regarding time to onset of symptoms and pattern of tumor growth. Infiltration of the tumor tissue with ED-1+ monocytes and macrophages, and CD8+ lymphocytes, however, was slightly increased in IL-2 treated animals. In a second experiment 4 non tumor-bearing Wistar rats were intracisternally injected with a single dose of 10(5) IU IL-2. These animals also showed slightly enhanced leptomeningeal infiltration with CD8+ lymphocytes compared to controls. We conclude that intrathecal application of high-dose IL-2 although eliciting a slight immune reaction within the leptomeninges does not inhibit leptomeningeal tumor growth or prolong symptom-free survival in our animal model of LM. These results raise doubt about the clinical efficacy of intrathecal IL-2 treatment in patients with LM.
Herrlinger
U
U
Department of Neurology, University of Tuebingen, Germany.
Buchholz
R
R
Jachimczak
P
P
Schabet
M
M
D000818:Animals; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D005910:Glioma / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D007278:Injections, Spinal; D007376:Interleukin-2 / Q000627:therapeutic use*; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis; D014185:Transplantation, Isogeneic; D014410:Tumor Stem Cell Assay
D007376:Interleukin-2; D016212:Transforming Growth Factor beta