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ABSTRACT: Immunotherapy of C3H/HeJ mammary adenocarcinoma with
interleukin-2, mistletoe lectin or their combination
[10/05/2001; European Journal of Cancer]
Clinical application of interleukin (IL)-2-based immunotherapy
of cancer has been limited by a major side-effect known as `capillary
leak syndrome', resulting from nitric oxide (NO) overproduction.
A galactoside-specific lectin from Viscum album L. (VAA) has
been reported to induce certain lymphokines and upregulate IL-2
receptors on lymphocytes.
Present study was, therefore, designed
to compare the effects of combination therapy with IL-2 (104
Cetus units/mouse, intraperitoneal (i.p). every 8 h, given as
5 day rounds per week, for one or two rounds) and VAA (1 ng/kg
subcutaneous (s.c.), biweekly) with those of IL-2 or VAA therapy
alone in C3H/HeJ female mice bearing s.c. transplants of a highly
metastatic C3L5 mammary adenocarcinoma.
IL-2 therapy alone reduced
tumour growth and metastasis, but caused significant water retention
indicative of capillary leakage in the kidneys after both rounds
of therapy, whereas pleural effusion was only evident after the
first round and not the second round.
A sharp rise in the systemic
NO levels after the first round, followed by a decline after
the second round of IL-2 therapy suggested a causal relationship
of increased NO levels to pleural effusion. A strong immunostaining
for nitrotyrosine (a marker for the production of peroxynitrite)
was noted in the renal tubules at the end of both rounds of therapy
suggestive of a causal association of this toxic NO-metabolite
with capillary leakage in the kidneys.
Addition of VAA to IL-2
therapy had no effect on any of the above parameters. Unexpectedly,
however, VAA therapy alone stimulated tumour growth as well as
lung metastases.
NO induction in the C3L5 cells by VAA was excluded
as a possible reason for this stimulation. Present results suggest
the need for exercising caution in the use of VAA as an immunoadjuvant
in human cancer therapy.
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