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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

From: Effects of cytarabine on activation of human T cells – cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic 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