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Abraham Solomon, Dilek Dursun, Zuguo Liu, Yuhuan Xie, Angelo Macri, Stephen C. Pflugfelder; Pro- and Anti-inflammatory Forms of Interleukin-1 in the Tear Fluid and Conjunctiva of Patients with Dry-Eye Disease. Invest. Ophthalmol. Vis. Sci. 2001;42(10):2283-2292.
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purpose. To compare the expression of the pro- and anti-inflammatory forms of
interleukin (IL)-1 in the tear fluid and conjunctival epithelium of
normal eyes and those with dry-eye disease.
methods. The concentrations of IL-1α, IL-1β (precursor and mature forms),
and IL-1 receptor antagonist (IL-1Ra) were measured by ELISA in tear
fluid samples obtained from normal individuals and patients with dry
eye who had rosacea-associated meibomian gland disease (MGD) or
Sjögren’s syndrome (SS) aqueous tear deficiency (ATD). These
cytokines were also measured in normal tear fluid before and after
nasal stimulation to induce reflex tearing. The relative expression of
these cytokines was evaluated in conjunctival impression cytology
specimens and conjunctival biopsy tissue obtained from normal subjects
and SS ATD–affected patients using immunofluorescent staining. Matrix
metalloproteinase (MMP)-9 concentration and activity in the tear fluid
were evaluated with gelatin zymography and with an MMP-9 activity assay
results. Compared with normal subjects, the concentration of IL-1α and mature
IL-1β in the tear fluid was increased, and the concentration of
precursor IL-1β was decreased in patients with MGD
(P < 0.05, P = 0.02, and P < 0.01, respectively) and SS ATD
(P < 0.001, P = 0.02, and P < 0.001, respectively). There was no significant
change in the concentration of IL-1α, precursor IL-1β, and IL-1Ra
in reflex tear fluid, indicating that the lacrimal glands may secrete
these cytokines. The activity of MMP-9, a physiological activator of
IL-1β, was significantly elevated in the tear fluid of both dry-eye
groups compared with normal subjects. A strong positive correlation was
observed between the intensity of corneal fluorescein staining and the
tear fluid IL-1α concentration (r 2 =
0.17, P < 0.02) and the mature-to-precursor
IL-1β ratio (r 2 = 0.46, P < 0.001). Positive immunofluorescent staining
for IL-1α, mature IL-1β, and IL-1Ra was observed in a significantly
greater percentage of conjunctival cytology specimens from eyes with SS
ATD than in those from normal eyes (P < 0.01 for
IL-1α, P < 0.009 for mature IL-1β, and P < 0.05 for IL-1Ra).
conclusions. Dry-eye disease is accompanied by an increase in the proinflammatory
forms of IL-1 (IL-1α and mature IL-1β) and a decrease in the
biologically inactive precursor IL-1β in tear fluid. Increased
protease activity on the ocular surface may be one mechanism by which
precursor IL-1β is cleaved to the mature, biologically active form.
The conjunctival epithelium appears to be one source of the increased
concentration of IL-1 in the tear fluid of patients with dry-eye
disease. These results suggest that IL-1 may play a key role in the
pathogenesis of keratoconjunctivitis sicca.
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