Drug modification of LPS-stimulated human monocyte-derived dendritic cells

Many drugs have been reported to convert dendritic cells (DCs) into a tolerogenic phenotype in vitro. However, there is evidence that an additional stimulus, such as lipopolysaccharide (LPS), may also be necessary for tolerogenic function in vivo. Little is known concerning the effects of drug modification on LPS-prestimulated DCs. In this study, monocyte-derived immature DCs were stimulated with LPS first and the influence investigated of six different agents on surface antigen expression, cytokine production and lymphocyte proliferation and cytotoxicity. Mycophenolic acid- and rapamycin-exposed DCs had little effect on surface antigen expression or functional activity towards lymphocytes. In contrast, treatment of immature dendritic cells with aspirin, dexamethasone, 1alpha,25-dihydroxyvitamin D3 (VD3) or butyric acid was associated with diminished expression of CD1a, CD1c, CD40, CD80 and CD83. Dendritic cell modification by aspirin, dexamethasone and VD3 were all associated with decreased production of tumour necrosis factor-alpha (TNFalpha). Furthermore, VD3 treatment was associated with a consistent and significant elevation of IL-6 production. Aspirin-, dexamethasone- VD3- and butyric acid-modified DCs suppressed interferon-gamma production, proliferation and cytotoxicity in co-culture with allogeneic mononuclear cells, but inconsistent results were obtained with different allogeneic combinations. Different drugs show varying effects on DC phenotype. No single agent was consistently effective in suppressing the stimulation of allogeneic mononuclear cells and future work is needed to explore drug combinations.