Correlations between tear cytokines, chemokines, and soluble receptors and clinical severity of dry eye disease.
OBJECTIVE
To determine cytokine and chemokine concentrations in the tears of patients with dry eye disease (DED) and analyze the possible relationships with the clinical severity of DED.


METHODS
Patients were examined using the Ocular Surface Disease Index, corneal and conjunctival staining, tear breakup time, and impression cytology. They were divided into four groups according to the Dry Eye Workshop severity classification. Tears were collected from 133 patients with DED and 70 healthy controls. Concentrations of cytokines, chemokines, and soluble receptors in collected tear samples were analyzed using current technology with a Human Cytokine/Chemokine kit, a Human Cytokine/Chemokine Panel, and a Human Soluble Cytokine Receptor Panel.


RESULTS
The levels of cytokines interleukin (IL)-1β (P < 0.05), IL-6 (P < 0.001), IL-16 (P < 0.001), IL-33 (P < 0.05), G-CSF (P < 0.001), and transforming growth factor (TGF)-α (P < 0.05) were significantly higher in patients with DED, whereas those of cytokines IL-4 (P < 0.001), IL-12 (p40) (P < 0.001), IL-17A (P < 0.05), and interferon-γ (P < 0.001) were significantly lower. The levels of Fractalkine (chemokine [C-X3-C motif] ligand 1; CX3CL1), MCP-1 (chemokine [C-C motif] ligand 2; CCL2), MIP-1δ (chemokine [C-C motif] ligand 15; CCL15), and ENA-78 (chemokine [C-X-C motif] ligand 5; CXCL5) (P < 0.001, respectively) and soluble receptors, sIL-1RI (P < 0.05), soluble glycoprotein (sgp) 130 (P < 0.05), sIL-6R (P < 0.001), soluble epidermal growth factor receptor (P < 0.05), and soluble tumor necrosis factor receptor 2 (P < 0.001), were higher in patients with DED. There were significant correlations between these molecules and the clinical severity of DED.


CONCLUSIONS
Fifteen molecules were elevated in the tears of patients with DED; four molecules were decreased. Although the levels of sIL-6R, sIL-6R, and sgp130 may be potential indicators of the homeostatic process, an increase in the levels of IL-6 and IL-1 β are the earliest observable changes in patients with DED. Further study on the biomarkers in the pathogenesis of DED and treatment target modalities would be needed.
Department of Health Promotion Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kyung-Sun
KS
Na
Jee-Won
JW
Mok
Ja Yeon
JY
Kim
Chang Rhe
CR
Rho
Choun-Ki
CK
Joo
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015352:Dry Eye Syndromes / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*; D013666:Tears / Q000737:chemistry*
D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D007371:Interferon-gamma