Sjögren's Syndrome (SS) is characterized by lymphocytic infiltration, destruction and dysfunction of the lacrimal and salivary glands and the presence of serum autoantibodies. Although, approximately 0.5% of the population suffers from SS, there is a female predominance of 9:1 compared with males. Most women with SS are postmenopausal; however, not all women who are post-menopausal develop SS. Therefore, we postulate that a decrease in the circulating levels of hormones creates an environment favorable to the development of SS in a predisposed genetic background.

In order to carry out our studies, we used the NOD.B10.H2^b mouse model of SS, and ovariectomized (OVX) them as a model for the post-menopausal condition. We removed the lacrimal glands and measured the gene expression and protein levels of several cytokines and chemokines known to be upregulated in patients with SS such as: IL-1β, IL-10, INF-γ, TNF-α, CCL9 and CXCL13. We also stained for markers of B cells (B220+) and T cells (CD4+ and CD8+), and counted positively stained cleaved caspase-3 cells as an indication of apoptosis. These experiments were done 3, 7 and 21 days post-OVX and compared to sham operated animals. In order to determine whether the changes observed with OVX were triggered mainly by a genetic pre-disposition, a non-prediposed OVX and sham operated mouse (C57BL/10) was used as control.

We found that gene expression of IL-1β, IL-10 and IFN-γ were upregulated in the lacrimal glands of the OVX NOD.B10.H2^b mice at 3 days post-OVX compared with sham operated animals. Gene expression of IL-1β, IL-10, IFN-γ, TNF-α, CCL9 and CXCL13, and protein levels of IL-1β, IL-10 and CCL9 were upregulated in the OVX NOD.B10.H2 ^b mice at 7 days post-OVX compared to sham operated animals. Also, at 7 days, an increase in B220⁺ B cells and an increase in cleaved caspase-3 were also observed in the OVX NOD.B10.H2^b mice lacrimal glands compared to sham operated animals. At 21 days, protein levels of IL-10 were also highly upregulated in the OVX NOD.B10.H2 ^b mice, together with an increase of B220⁺ B cells, a slight increase in the CD4/CD8 ratio and an increase on the number of caspase-3 positive cells. No changes were observed in any of the above parameters measured in the OVX C57BL/10 mice compared to the sham operated group, supporting our hypothesis that both, genetics and a decrease in the levels of hormones are necessary for SS to occur.