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

Objectives-It was noted that treatment of a patient with acute mania by hal operidol was associated with marked improvement in activity of rheumatoid a rthritis. The objective of this study was to examine the effects of haloper idol 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 cytokin es interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alph a) was measured in bacterial lipopolysaccharide stimulated whole blood cult ures 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 b oth IL1 beta and TNF alpha in vitro in a dose dependent manner and over a p rolonged time period. Marked inhibition was seen over a range of concentrat ions of haloperidol from 0.5 mu g/ml to 50 mu g/ml, including those predict ed to occur in the patient's blood. Conclusions-Haloperidol treatment seemed to alleviate inflammation in rheum atoid arthritis. In vitro experiments would suggest that the mechanism is b y direct inhibition of proinflammatory cytokine release. This phenomenon re quires further investigation and may potentially lead to the development of novel treatment.