Rheumatology Advance Access originally published online on December 8, 2004
Rheumatology 2005 44(4):449-455; doi:10.1093/rheumatology/keh506
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Rheumatology Vol. 44 No. 4 © British Society for Rheumatology 2004; all rights reserved
Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase
1 Clinical Dental Sciences and 2 Immunology, University of Liverpool, Liverpool, UK.
Correspondence to: L. J. Dawson. E-mail: ldawson{at}liv.ac.uk
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.
KEY WORDS: Sjögren's syndrome, Cholinesterase, Salivary acinar cells, Calcium, Hydroxychloroquine
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