Figure 1

Synergistic anti-inflammatory activity of prednisolone and dipyridamole in vitro. (a) Dipyridamole and prednisolone were diluted orthogonally using a twofold serial dilution, and then combined to produce a drug combination dose-response matrix. The dose responses for prednisolone and dipyridamole as individual agents are located in the bottom row and left column, respectively. Combination doses fill out the matrix and component concentrations can be read from the row and column labels. The combination dose-response matrix was applied to lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), and tumor necrosis factor (TNF)-α in the supernatant was measured by ELISA after 18 hours. Percentage inhibition of TNF-α secretion relative to vehicle-treated controls is indicated in each cell of the matrix and represented by a color scale, where warm colors indicate more inhibition (left). Isobolographic analysis of the inhibition matrix (blue line) compares the activity of the combination with a theoretical additive interaction (red line) at the 70% inhibition level (right). Synergistic interactions fall below the additivity threshold and approach the origin, and an antagonistic interaction would lie above the red additivity line. (b) Combination matrices were measured including a fixed dose of RU486 at the indicated concentration at each point in the corresponding dose response matrix. Percentage inhibition of LPS-induced TNF-α secretion relative to vehicle-treated controls is indicated in each cell of the matrix.