Table 1 A summary of pharmacological effects on T cell activation; studies of high cytarabine concentrations alone, low cytarabine levels and low cytarabine levels in combination with ATRA and/or valproic acid
Parameter | High cytarabine levels (44 and 1.0 μM) | Low cytarabine levels (0.35 and 0.01 μM) | Low cytarabine levels (0.35 and 0.01 μM) combined with ATRA 1 μM and/or valproic acid (500 and 1000 μM) |
|---|---|---|---|
T cell viability | Decreased, apoptosis induction | Decreased only for 0.35 μM | No significant effect for most combinations |
T cell proliferation | Decreased | Decreased only for 0.35 μM | A highly significant decrease for combinations with cytarabine 0.35 μM |
CD4:CD8 ratio | Decreased | No effect | No effect |
CD69 expression | Prolonged expression, especially for CD8+ but also CD4+ cells | No effect both for CD4+ and CD8+ cells | CD4+ cells: Increased by ATRA and decreased by valproic acid, no effect when combining these two drugs. The ATRA effect maintaining when combined with cytarabine. CD8+ cells: Increased by ATRA and valproic acid, the increase was also seen in combinations with cytarabine. |
CD38 expression | No effect | No effect both for CD4+ and CD8+ cells | CD4+ cells: Increased by ATRA and decreased by valproic acid, the ATRA effect maintained in the presence of cytarabine. CD8+ cells: Increased by ATRA and decreased by valproic acid, the ATRA effect maintained in combinations. |
FasL release | Decreased | No effect | Strong decrease in all combinations also with cytarabine 0.01 μM |
TRAIL release | Minor decrease only at 44 μM | No effect | Minor effects |
HSP90 release | Decreased | No effect | Strong decrease both for cytarabine 0.35 and 0.01 μM |
HSP70 | Increased | No effect | No effect for all except one combination |
Cytokine release; hierarchical cluster analysis including 24 soluble mediators | Decreased levels for two out of 4 main clusters including 9 cytokines, including the cluster showing decreased levels for the drug combinations. | Only minor effects | Decreased levels only for one out of the four main clusters, including 4 cytokines |