Local expression of tumor necrosis factor-receptor 1:immunoglobulin G can induce salivary gland dysfunction in a murine model of Sjogren's syndrome
IntroductionTumor necrosis factor (TNF) is a pleiotropic cytokine with potent immune regulatory functions. Although TNF inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjogren's syndrome (SS).
The aim of this study was to assess the effect of a locally expressed TNF inhibitor on the salivary gland (SG) function and histopathology in an animal model of SS.
Methods: Using in vivo adeno-associated viral gene transfer, we have stably expressed soluble TNF-receptor 1-Fc fusion protein locally in the SGs in the Non Obese Diabetic (NOD) model of SS. Pilocarpine stimulated saliva flow was measured to address the SG function and SGs were analyzed for focus score and cytokine profiles.
Additionally, cytokines and autoantibody levels were measured in plasma.
Results: Local expression of TNF-receptor 1:immunoglobulin G (TNFR1:IgG) fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of Tumor Growth Factor (TGF)-beta1 and decreased levels of interleukin (IL)-5, IL-12p70 and IL-17 were detected in the SGs.
In contrast, plasma levels showed significantly decreased levels of TGF-beta and increased levels of IL-4, interferon (IFN)-gamma, IL-10 and IL-12p70.
Conclusions: Our findings suggest that expression of TNF inhibitors in the SG can have a negative effect on SG function and that other cytokines should be explored as points for therapeutic intervention in SS.
Author: Jelle VostersHongen YinNienke RoescherMarc KokPaul TakJohn Chiorini
Credits/Source: Arthritis Research &Therapy 2009, 11:R189
Published on: 2009-12-14
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