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

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.