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

Objective. To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren'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 K-i 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 K-i for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 mu M. 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.