Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines

Objectives-It was noted that treatment of a patient with acute mania by haloperidol was associated with marked improvement in activity of rheumatoid arthritis. The objective of this study was to examine the effects of haloperidol on inflammatory cytokine release in vitro, as a potential mechanism to explain the in vivo antiinflammatory effects of haloperidol. Methods-The effect of haloperidol on the production of inflammatory cytokines interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) was measured in bacterial lipopolysaccharide stimulated whole blood cultures and on the promonocyte cell line THP-1, using commercial and in house enzyme linked immunosorbent assays to measure cytokine concentrations. Results-Haloperidol inhibited lipopolysaccharide stimulated production of both IL1 beta and TNF alpha in vitro in a dose dependent manner and over a prolonged time period. Marked inhibition was seen over a range of concentrations of haloperidol from 0.5 mu g/ml to 50 mu g/ml, including those predicted to occur in the patient's blood. Conclusions-Haloperidol treatment seemed to alleviate inflammation in rheumatoid arthritis. In vitro experiments would suggest that the mechanism is by direct inhibition of proinflammatory cytokine release. This phenomenon requires further investigation and may potentially lead to the development of novel treatment.