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Driss Zoukhri, Robin R. Hodges, Dosek Byon, Claire Larkin Kublin; Role of Proinflammatory Cytokines in the Impaired Lacrimation Associated with Autoimmune Xerophthalmia. Invest. Ophthalmol. Vis. Sci. 2002;43(5):1429-1436.
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purpose. To determine the effects of the proinflammatory cytokines interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α on neurally mediated lacrimal gland protein secretion and to determine whether the amount of IL-1β protein is upregulated in inflamed lacrimal glands of the MRL/lpr mouse, a murine model of human Sjögren syndrome.
methods. Lacrimal gland lobules of BALB/c mice were prepared and incubated for 2 hours in the presence or absence of recombinant human (rh)IL-1α, rhIL-1β (10 ng/mL each), or rhTNFα (50 ng/mL). Peroxidase secretion in response to depolarizing KCl (75 mM) solution was measured by spectrofluorometric assay. In another set of experiments, saline, rhIL-1β (1 μg), or an antibody against IL-1 receptor type I (IL-1RI), with or without rhIL-1β, was injected (2 μL) into the lacrimal glands of anesthetized BALB/c mice. Twenty-four hours later, lacrimal gland lobules were prepared and peroxidase secretion was measured. The amount of IL-1β protein in lacrimal gland acinar cell lysates prepared from 3-, 9-, and 13-week-old BALB/c, MRL/+, and MRL/lpr mice was determined by ELISA.
results. KCl-induced peroxidase secretion was inhibited in vitro 62%, 66%, and 53% by rhIL-1α, rhIL-1β, and rhTNFα, respectively. In vivo, rhIL-1β inhibited KCl-induced peroxidase secretion by 72%. This inhibitory effect of IL-1β was completely reversed by an antibody against IL-1RI. Compared with 3-week-old mice, the amount of IL-1β protein was upregulated 15- and 21-fold in lacrimal gland acinar cells isolated from 9- and 13-week-old MRL/lpr mice, respectively.
conclusions. Proinflammatory cytokines inhibit neurally mediated lacrimal gland secretion. The amount of IL-1β protein is upregulated in acinar cells prepared from lacrimal glands infiltrated with lymphocytes. These results suggest that elevated levels of IL-1β, as they occur in Sjögren syndrome exocrine glands, may impair the secretory function of these tissues.
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