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Dexamethasone Mediated Inhibition of Local IL-2 Immunotherapy is Dose Dependent
in Experimental Brain Tumors
Maciej S. Lesniak,
Patrick Gabikian,
Betty M. Tyler,
Drew M. Pardoll,
Henry Brem
Division of Neurosurgery, The University of Chicago Hospitals, Chicago, IL; The
University of Chicago Hospitals, Neurosurgery, MC 3026, 5841 S. Maryland Avenue,
Chicago, IL 60637, USA; Tel.: +1-773-702-2123; Fax: +1-773-702-3518; E-mail: mlesniak@surgery.bsd.uchicago.edu
[M.S.L.].
Department of Neurosurgery, The Johns Hopkins School of Medicine, Baltimore, MD,
USA [H.B.]. Department of Oncology, The Johns Hopkins School of Medicine, Baltimore,
MD, USA [P.G., B.M.T., D.M.P.,
H.B.].
Local
delivery of cytokines has been shown to have a potent anti-tumor activity
against a wide range of malignant brain tumors.
In this study, we examined the
role of systemic immunosuppression using dexamethasone on the efficacy of local
IL-2 immunotherapy in treating experimental murine CNS tumors.
An
endothelial cell line secreting hIL-2 (NTC-121) was injected intracranially in
C57BL/6 mice (n = 10/group) along with B16/F10 (wild type) melanoma cells.
A separate
set of animals also received daily injections of either 1 mg/k or 10 mg/kg of
dexamethasone.
Sixty percent of mice treated with IL-2 (P
< 0.001 vs. control) vs. 55% (P
< 0.005) of mice treated with IL-2 and 1 mg/kg of dexamethasone were
long-term survivors (LTS) of >120
days.
There was no difference in survival between control animals that received
only wild type cells or animals that were treated with IL-2 and 10 mg/kg of
dexamethasone.
Histopathological examination of brains from animals sacrificed
at different times showed an accumulation of CD8 + T-cells around the site of
the injected tumor only in the IL-2 group and the group that received 1 mg/kg of
dexamethasone.
These
results suggest that while high doses of dexamethasone can completely inhibit
the immune response observed with IL-2, lower and more likely therapeutic doses
of dexamethasone do not inhibit local IL-2 immunotherapy.
Keywords: brain tumors, dexamethasone, histopathology, immunohistochemistry,
immunotherapy, interleukins, steroids
Copyright ©
2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/123/A/6/abstract.htm
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