The impact of clozapine on regulation of inflammation in murine macrophage cells.

OBJECTIVES: Clozapine is an atypical antipsychotic drug known for its impact on production of pro-inflammatory cytokines. The aim of our work was to examine the impact of clozapine on the production of interleukin 6 (IL-6) by the LPS (lipopolysaccharide) stimulated macrophage cells and to confirm or exclude that it regulates the inflammation due to its interaction with alpha 7 nicotinic receptor (nAChR). Secondly, we focused on a verification of the antioxidant effect of clozapine.

METHODS: The levels of IL-6 in cell culture media were determined by ELISA method. Antioxidant properties of clozapine were estimated based on the reduction of 2,2-diphenyl-1-picrylhydrazyl radical.

RESULTS: The IL-6 level produced by cells treated clozapine decreased significantly from IL-6 level created by clozapine-untreated cells. However, the production of IL-6 in the cells treated with clozapine and simultaneously with selective alpha 7 nAChR antagonist methyllycaconitine did not alter significantly from the IL-6 production in the cells treated just with clozapine. The free radical scavenging activity of clozapine in concentration 1.00 mM was found equivalent to 0.13 mM of standard antioxidant N-acetyl-L-cystein.

CONCLUSION: Our study confirmed, that clozapine reduces production of IL-6 in LPS-activated macrophage cells nevertheless we denied that it would be mediated through alpha 7 nAChR. Moreover antioxidant potential of clozapine was observed.