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Abstract

The tear film plays an important role in the defense of the external ocular surface. During sleep a number of changes take place, including increased production and release of various inflammatory mediators. We have studied the hypothesis that closed-eye tears contain proinflammatory cytokines and lipid inflammatory mediators, which serve to recruit polymorphonuclear leukocytes (PMNs) and regulate the function of PMNs and IgA during sleep. We investigated interleukin-1beta, interleukin-6, interleukin-8, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor (GM-CSF), leukotriene B4 (LTB4), and platelet activating factor (PAF) in open and closed-eye tears of normal healthy subjects. Results showed that IL-6, IL-8, GM-CSF, LTB4, and PAF were present in high levels in closed-eye tears compared to open-eye tears. Closed-eye tears were able to recruit neutrophils, with maximal recruitment after 8 hr of sleep, suggesting that chemokine IL-8 and the lipid chemoattractant LTB4 were active. Flow cytometric analysis revealed that incubation of neutrophils with closed-eye tears up-regulated the surface expression of IgA receptor, indicating that the GM-CSF in tears was functionally active. Up-regulation of cytokines and the lipid inflammatory mediator LTB4 during eye closure are noteworthy, as each of these cytokines has an established role in initiation and amplification of the inflammatory response. IL-8 and LTB4 may act as potent chemoattractants and activators for PMNs, whereas IL-6 and GM-CSF potentiate the secretion and function of IgA and enhance neutrophil responsiveness to proinflammatory agonists.

Effects of Awakening and the Use of Topical Dexamethasone and Levofloxacin on the Cytokine Levels in Tears Following Corneal Transplantation

“…We found that the levels of IL-10, IL-13, IL-17, IFN γ , and CCL5 were lower in the closed-eye tears, while the level of CXCL8 was higher at eye opening when compared to the values measured 30 mins later. These findings are in line with numerous studies showing alterations in tear fluid composition after awakening [ 1 , 3 , 10 , 14 , 16 , 17 ]. During sleep or eye closure, physiological changes occur in the ocular surface causing a local subclinical inflammatory state [ 1 , 16 ].…”

“…A specific diurnal alteration pattern of IL-1 β , IL-6, CXCL8, IL-10, IL-12p70, and TNF α has been found showing the importance of the timing of tear collection during the day [ 2 ]. It is noteworthy that the examination of different cytokines present in overnight tears has been reported mainly in control [ 1 , 10 ] and allergic eyes [ 14 ].…”

Dry Eye as a Mucosal Autoimmune Disease

“…In addition, PD-L1 protects the ocular surface from T-cell-mediated damage in murine models of corneal transplant and dry eye disease [62–65]. However, decreased tear production and clearance during disease of the LFU or in the closed eye during sleep cause the levels of inflammatory mediators in tears to increase, which may compromise ocular surface homeostasis [53,66,67]. …”

Dry Eye Disease and Microbial Keratitis: Is There a Connection?

“…This may relate to factors mentioned above or could result from the combination of tear film alteration by the contact lens and tear film changes that take place in a closed-eye situation. 68–71 Both appear to be independent factors that occur during lid closure; however, the relationship between the two is not as well defined. A contact lens, regardless of material, will alter the environment and therefore the ocular surface when worn on a regular basis.…”