Supra-therapeutic plasma concentrations of haloperidol induce moderate inhibition of lipopolysaccharide-induced interleukin-8 release in human monocytes.

BACKGROUND

The clinical use of antipsychotics and mood-stabilizing drugs with proven efficacy is largely determined by the occurrence of treatment-emergent adverse events and routine clinical chemistry and haematology data, which together define the safety and tolerability profile of these psychopharmaceuticals. Whereas the effects of mood-stabilizing drugs on functional properties of blood cells have been poorly investigated, the effects of antipsychotics have received more attention. Such studies have yielded conflicting results. This study examined the effects of the mood-stabilizing drugs carbamazepine and valproic acid and of the antipsychotic drugs olanzapine, risperidone and haloperidol on the production of the pro-inflammatory chemokine interleukin-8 (IL-8), which is released from human monocytes when activated by Gram-negative lipopolysaccharide (LPS).

METHODS

Peripheral human whole blood was diluted with Roswell Park Memorial Institute (RPMI) cell culture medium and stimulated with LPS. Accumulating IL-8 was quantified in the supernatant with an adapted enzyme-linked immunosorbent assay (ELISA) and the results correlated to the number of monocytes at venipuncture.

RESULTS

At supra-therapeutic concentrations of 100 µM, haloperidol inhibited the LPS-induced release of IL-8 in peripheral human monocytes moderately, whereas olanzapine, risperidone, carbamazepine and valproic acid showed no such effect.

CONCLUSIONS

The results suggest that these mood-stabilizing drugs and antipsychotics are endowed with clinically favorable inertness rather than pro-inflammatory properties.