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J. D. Pitcher, III, C. S. De Paiva, S. B. Pangelinan, E. Rahimy, W. J. Farley, M. E. Stern, D. Q. Li, S. C. Pflugfelder; Pharmacological Cholinergic Blockade Stimulates Inflammatory Cytokine Production in the Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4241.
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To investigate the effects of cholinergic blockade on inflammatory cell infiltration and cytokine production in the lacrimal gland (LG).
C57BL/6 mice received subcutaneous injection of scopolamine (SCOP) QID for 5 days. Tear production was measured by cotton thread test. LG fuction was determined by tear peroxidase level quantification. Extraorbital LGs were surgically excised and prepared either for histology or lysed for genetic analysis. Immunohistochemistry in LG frozen sections evaluated immunophenotype of infiltrating cells (CD4, CD8a, CD11c, CD11b, CD45, CD45RA, CD103, and γΔTCR). EGF, Th-1, -2 and -17 associated cytokines in lacrimal glands were evaluated by real time PCR.
Tear production could not be measured up to two hours post SCOP injection. Mice receiving SCOP developed a significant increase in number of CD4+ T and CD8+T cells infiltrating the LG compared to untreated controls. The number of CD11c, CD11b, CD45, and CD103 positive cells also increased significantly. EGF mRNA levels decreased in mice subjected to pharmacological blockage, indicating a decrease in LG function. IL-6, TGF-β1&2, IFN-γ, IL-12, IL-2, IL-23R, IL-17R, T-bet, IL-12rb1, and IL-18R transcripts levels were found to be significantly elevated in SCOP treated animals compared to untreated controls.
Pharmacological blockade of lacrimal secretion induced a significant CD4+ infiltration, mimicking Sjögren’s syndrome. The cytokine profile included a mix of Th-17 and Th-1 cytokines.
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