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 eVects of haloperidol on inflammatory cytokine release in vitro, as a potential mechanism to explain the in vivo antiinflammatory eVects of haloperidol. Methods-The eVect of haloperidol on the production of inflammatory cytokines interleukin 1 (IL1 ) and tumour necrosis factor (TNF ) 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 and TNF 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 µg/ml to 50 µg/ml, including those predicted to occur in the patient's blood. Conclusions-Haloperidoltreatmentseemed 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. (Ann Rheum Dis 1999;58:585-587) Proinflammatory cytokines such as tumour necrosis factor (TNF ) and interleukin 1 (IL1 ) are intimately involved in the pathological process of rheumatoid arthritis (RA) 1 and may be useful targets for treatment. 2 We observed a dramatic improvement of RA in a patient taking the major tranquiliser haloperidol. On in vitro examination, this drug was able to reproducibly suppress both TNF and IL1 production from a variety of cells using commercial or in house enzyme linked immunosorbent assays (ELISAs). This highlights the intimate relation between neuroendocrine and immune systems and may provide the basis for novel drug design in RA. Case reportA 32 year old woman with stable seropositive RA controlled by non-steroidal anti-inflammatory drugs (NSAIDs) was admitted with acute mania. She was coincidentally noted to have extensive active synovitis involving the small joints of the hands and feet, together with knees and wrists, and early morning stiVness lasting until the evening. Markers of inflammation in the blood were raised with an erythrocyte sedimentation rate (ESR) of 65 mm 1st h and C reactive protein (CRP) 90 mg/dl. These clinical and laboratory features remained after two days of observation, and continued administration of NSAID. Oral haloperidol at a dose of 5 mg twice a day was then started to control the mania. Over the next two days not only did her mood normalise, but also the synovitis markedly resolved in her hands, wrists and knees. The CRP dropped in parallel to 20 mg/ml. During this time, the patient noticed that her early morning stiVness was limited to only approximately 90 minutes.Haloperidol was gradually stopped over the nex...

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