Inflammatory stimuli accelerate Sjögren's syndrome-like disease in (NZB x NZW)F1 mice.
OBJECTIVE
This study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice.


METHODS
Female (NZB x NZW)F1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine-induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland-infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60.


RESULTS
While IFA-treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS-treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA-treated mice showed significantly higher frequencies of CD11clow, B220+, Ly6C+, mouse PDCA-1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA-treated mice had higher levels. The gland dysfunction observed in IFA-treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland.


CONCLUSIONS
Our data suggest that generalized inflammatory stimuli can accelerate the development of SS-like disease in (NZB x NZW)F1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response.
Deshmukh
Umesh S
US
University of Virginia, Charlottesville, VA 22908, USA.
Ohyama
Yukiko
Y
Bagavant
Harini
H
Guo
Xiaoti
X
Gaskin
Felicia
F
Fu
Shu Man
SM
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D005620:Freund's Adjuvant / Q000494:pharmacology; D007249:Inflammation; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D008814:Mice, Inbred NZB; D012469:Salivary Glands / Q000503:physiopathology; D012859:Sjogren's Syndrome / Q000276:immunology*
D001323:Autoantibodies; D008055:Lipids; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant