E. Oelmann et al., INTERLEUKIN-1 RECEPTOR ANTAGONIST INHIBITS GROWTH MODULATION OF HUMANTUMOR-CELL LINES BY INTERLEUKIN-1 IN-VITRO, International journal of oncology, 4(3), 1994, pp. 555-558
In this study we report that recombinant human (rh) interleukin-1alpha
(IL-1alpha) has direct and dose-dependent growth-modulating effects o
n human tumor cell lines in vitro as measured by a human tumor cloning
assay (HTCA). Colony formation of the melanoma cell line A 375 was in
hibited by rhIL-1alpha, whereas colony formation of the glioblastoma c
ell line HTB 14 was enhanced by this cytokine. Both growth-modulating
effects were dose-dependent, however with some saturation. Subsequentl
y, we have tested the activity of recombinant human IL-1 receptor anta
gonist (rhIL-1ra) on the tumor growth modulation by rhIL-1alpha. Tumor
cells were incubated with increasing concentrations of rhIL-1ra and t
hen added to the cultures containing rHIL-1alpha. Concentrations of rh
IL-1ra were chosen to achieve a range between 0.01 and 100 ng/ml which
includes a 1000-fold molar excess over IL-1alpha. The receptor antago
nist was able to block both the inhibition and the stimulation of clon
al growth of the respective tumor cell line by rhIL-1alpha. Furthermor
e, there was a direct dose dependent relationship revealing higher IL-
1 antagonism of rhIL-1ra at higher concentrations with maximum efficac
y at 1000-molar excess concentrations over IL-1alpha. In addition, rhI
L-1ra alone did not reveal major modulation of the growth of A 375, bu
t significantly decreased colony formation of HTB 14. We conclude that
rhIL-1ra can counteract modulation of clonal growth of human tumor ce
lls by IL-1alpha in vitro. Since our report provides first evidence th
at the stimulation of clonal tumor cell growth by IL-1alpha can be blo
cked by rhIL-1ra, this member of the IL-1 cytokine network should be f
urther studied as a possible candidate for experimental cancer treatme
nt.