Ji. Azconaolivera et al., EFFECTS OF VOMITOXIN (DEOXYNIVALENOL) AND CYCLOHEXIMIDE ON IL-2, IL-4, IL-5 AND IL-6 SECRETION AND MESSENGER-RNA LEVELS IN MURINE CD4(+) CELLS, Food and chemical toxicology, 33(6), 1995, pp. 433
The effects of continuous in vitro exposure to the trichothecene, vomi
toxin (VT) or another protein synthesis inhibitor, cycloheximide (CHX)
, on interleukin (IL) secretion and mRNA levels were evaluated in muri
ne splenic CD4(+) cells. Significant increases were seen in supernatan
t IL-2, IL-4 and IL-5 obtained from 7 day Concanavalin A (Con A)-stimu
lated CD4(+) cultures containing VT concentrations of 250, 100 and 100
ng/ml, respectively, compared with controls run in the absence of VT.
The effect of VT on CD4(+) cell proliferation was also assessed after
culturing for 3, 5 and 7 days with Con A. Although total cell numbers
were not affected at day 3, cultures at day 5 with 50 or more ng VT/m
l and at day 7 with 100 or more ng VT/ml had significantly lower cell
numbers than controls. In addition, viable cell number was unaffected
at day 3, but was significantly decreased at day 5 by VT concentration
s of 12.5 ng or more mi and at day 7 by 100 or more ng VT/ml. Elevatio
ns in IL-2, IL-4 and IL-5 were also observed in 7-day Con A-stimulated
CD4(+) cell cultures containing CHX at 50-100, 50 and 10 ng/ml, respe
ctively. When CD4(+) cells were stimulated with Con A in the absence o
f inhibitors and then subjected to reverse transcriptase-polymerase ch
ain reaction coupled with Southern analysis, maximal IL-2, IL-4 and IL
-6 mRNA levels were induced at 48 hr whereas peak IL-5 mRNA was observ
ed at 72 hr. Superinduction of IL-2 mRNAs was observed in the presence
of VT at 50-100 ng/ml and CHX at 50-250 ng/ml. IL-4 and IL-5 mRNAs we
re superinduced by VT at 100 ng/ml and CHX at 50 ng/ml. The results su
ggest that VT and CHX could superinduce both interleukin secretion and
mRNA transcript levels in CD4(+) cell cultures and that, for VT, thes
e effects occurred concurrently with inhibition of cell proliferation.