Budesonide Modulates the Immune Cross-Talk between Mononuclear and Colon Cancer Cells

Background: The introduction of corticosteroids in the therapeutic armamentarium has been a great contribution to human health. Budesonide, a semi-synthetic glucocorticoid derivative gained its popularity due to its anti-inflammatory, immunosuppressive and even anti-carcinogenic properties. In this study we examine the effect of budesonide on the immune dialogue between peripheral blood mononuclear cells and colon carcinoma cells from two human lines. Methods: Unstimulated peripheral blood mononuclear cells or cells stimulated with either lipopolysaccharide or phorbol myristate acetate/ionomycin were incubated without or with budesonide at 10-8 M, 10-7 M and 10-6 M and the production of TNFα, IL-1β, IL-6, IFNγ, IL-2, IL-1ra and IL-10 was examined applying ELISA method. In another set of experiments peripheral blood mononuclear cells were co-cultured with HT-29 or RKO colon carcinoma cells in the absence or presence of budesonide and the secretion of the abovementioned cytokines was evaluated. Results: Budesonide caused reduced proliferation of peripheral blood mononuclear cells, HT-29 or RKO at 10-8 M as tested by XTT test, but had no effect at higher concentrations. The secretion of TNFα, IL-1β and IL-6 by non-stimulated peripheral blood mononuclear cells or cells stimulated with either lipopolysaccharide or cells from both colon cancer lines was inhibited upon incubation with budesonide at concentrations between 10-8 M and 10-6 M. The production of IL-2 by phorbol myristate acetate/ionomycin treated peripheral blood mononuclear cells or cells stimulated with HT-29 colon cancer cells was suppressed by budesonide, but IL-2 secretion by RKO stimulated peripheral blood mononuclear cells was not affected. Budesonide did not influence the secretion of IFNγ by non-stimulated peripheral blood mononuclear cells or by cells stimulated with PMA/ionomycin. However, HT-29 and RKO-induced production of IFNγ was inhibited by the three budesonide concentrations. Budesonide caused reduced secretion of IL-10 by non-stimulated peripheral blood mononuclear cells, or by cells stimulated with either lipopolysaccharide or RKO cancer cells, whereas that induced by HT-29 cells was not affected. IL1ra synthesis by non-stimulated peripheral blood mononuclear cells or cell stimulated with HT-29 colon cancer cells was inhibited upon 24 hrs incubation with budesonide, while that produced by lipopolysaccharide or RKO stimulated PBMC was not affected. Conclusions: It appears that the capacity of budesonide to modify the immune dialogue between mononuclear and certain types of cancer cells may be one of the ways by which this glucocorticosteroid may affect tumorigenesis.