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A. K. Mircheff, Y. Wang, P. B. Thomas, S. W. Song, T. Nakamura, D. Stevenson, J. E. Schechter, M. D. Trousdale; Dacryoadenitis in Rabbits Induced by Transient Local Prolactin Increase. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1914.
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Pregnancy appears to enhance mucosal immune function in the lacrimal gland (LG) as in the mammary gland. Ductal epithelial cells increase their content of prolactin (PRL) and express a novel endocrine secretory pathway for PRL; acinar cells accelerate transcytotic exocrine secretion of secretory component. Periductal lymphocytic foci decrease, while interacinar IgA+ plasmacytes and content of IgA increase. We hypothesize that mucosal immune function is associated with tolerance to autoantigens enforced by ACAID-like immunoregulatory networks. However, PRL induces TH1 effector responses, and elevated PRL is associated with Sjögren’s syndrome (SjS) and other autoimmune diseases. Since the physiological hyperprolactinemia of pregnancy is accompanied by elevated estradiol and progesterone, we used a replication-deficient adenovirus vector for rabbit PRL (AdPRL) to test the hypothesis that local elevation of PRL disrupts immunoregulation when it occurs outside the context of pregnancy-associated endocrine changes.
AdPRL (1 × 108 pfu in 0.1 ml) was injected into OS LG of mature female rabbits. Control LG were injected with AdGFP. OD LG were untreated. Ocular surface status was examined periodically. LG were collected at necropsy and prepared for H&E staining, immunohistochemistry, and real time RT-PCR. Two experiments were performed, each with 3 animals per treatment and post-injection interval.
PRL mRNA in AdPRL-injected glands increased maximally on d 4, decreased substantially by d 12, and returned to normal by d 29. mRNAs for the TH1 cytokines, IFN-γ and TNF-α, increased by d 4 but remained elevated on d 12 and had not yet returned to control values by d 29. OS Schirmer scores decreased by 50%, and Rose Bengal scores increased 3-fold. Glands were heavily infiltrated by CD18+ cells and T cells. In contrast, AdGFP-injection caused no change in PRL mRNA, slower and smaller changes in IFN-γ and TNF-α, no change in Schirmer scores, no increase in Rose Bengal staining above OD values, and only occasional, mild dacryoadenitis.
While the observed pathophysiological changes may have resulted from immune responses to either viral antigens or autoantigens, it is clear that transient elevation of local PRL greatly accelerated and amplified those responses. This result establishes that PRL significantly influences immunoregulation in the lacrimal gland, and it accords with the hypothesis that transiently elevated PRL is a factor in SjS pathogenesis.
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