Abstract
Purpose: :
SS is characterized by upregulation of several pro-inflammatory cytokines in the lacrimal glands. However, the source and time course of the cytokine increase remain to be elucidated. We have been studying the disease progression using ovariectomized (OVX) NOD.B10.H2b mouse, which provides a model of menopause and genetic predisposition to SS. We have shown that lymphocytic infiltration of the lacrimal gland significantly increases at 3, 7, 21 and 30 after OVX and this infiltration was prevented by physiological doses of 17β estradiol (E2) or dihydrotestosterone (DHT). In this study, we investigated the time course of changes in the levels of cytokines IL-1β, IL-4, TNF-α and IL-10 in the lacrimal glands following OVX. We also investigated whether treatment with E2 or DHT prevented the changes in cytokine levels found after OVX.
Methods: :
Six weeks old NOD.B10.H2b and C57BL/10 mice were sham operated, OVX, OVX+E2 or OVX+DHT for 3, 7, 21 and 30 days. At the end of each experimental time period, lacrimal glands were removed and homogenized. Protein concentration and cytokine levels were determined in the homogenate. Protein assays were performed using the Bradford method. The levels of IL-1β, IL-4, TNF-α and IL-10 were determined by ELISA (BD Biosciences).
Results: :
A significant increase in the levels of IL-1β, IL-4 and TNF-α was observed in the lacrimal glands of OVX NOD.B10.H2b mice compared to the sham operated groups in all four experimental times studied. IL-10 significantly increased only at 21 and 30 days after OVX. Treatment with E2 or DHT prevented the increase in levels of IL-1β, IL-4, TNF-α and IL- at all 4 experimental times. No significant differences were observed in the levels of these cytokines in the OVX C57BL/10 mice compared to sham operated groups at any of the experimental times.
Conclusions: :
Our results suggest that decreased levels of ovarian sex hormones upregulate the pro-inflammatory cytokines in the lacrimal gland of genetically predisposed mice and these effects were prevented with physiological doses of E2 or DHT. Thus, both hormonal and genetic effects seem to be necessary for the pathogenesis of the disease.
Keywords: cytokines/chemokines • lacrimal gland • autoimmune disease