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Rheumatology Advance Access published online on December 8, 2004
Rheumatology, doi:10.1093/rheumatology/keh506
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British Society for Rheumatology; all rights reserved
Received September 17, 2004
Accepted November 2, 2004

Original Papers

Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase

L. J. Dawson 1*, V. L. Caulfield 1, J. B. Stanbury 1, A. E. Field 1, S. E. Christmas 2, and P. M. Smith 1

1 Clinical Dental Sciences, University of Liverpool, Liverpool, UK
2 Immunology, University of Liverpool, Liverpool, UK

* To whom correspondence should be addressed.
L. J. Dawson, E-mail: ldawson{at}liv.ac.uk


  Abstract

Objective. To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjögren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity.

Methods. The Ellman method was used to determine the levels of salivary cholinesterase activity and the Ki of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca2+]i in mouse submandibular acinar cells was determined using fura-2 microfluorimetry.

Results. Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P<0.05) and stimulated saliva (P<0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca2+]i. The in vitro Ki for hydroxychloroquine inhibition of cholinesterase was 0.38 ± 1.4 µM.

Conclusion. These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Keywords: Sjögren's syndrome; Cholinesterase; Salivary acinar cells; Calcium; Hydroxychloroquine.
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