THE PROINFLAMMATORY CYTOKINES AND ARACHIDONIC-ACID METABOLITES IN HUMAN OVERNIGHT TEARS - HOMEOSTATIC MECHANISMS

The tear film plays an important role in the defense of the external o cular 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 proinflamma tory cytokines and lipid inflammatory mediators, which serve to recrui t polymorphonuclear leukocytes (PMNs) and regulate the function of PMN s and IgA during sleep. We investigated interleukin-1 beta, interleuki n-6, interleukin-8, monocyte chemotactic protein 1, granulocyte-macrop hage colony stimulating factor (GM-CSF), leukotriene B-4 (LTB4), and p latelet activating factor (PAF) in open and closed-eye tears of normal healthy subjects. Results showed that IL-6, IL-8, GM-CSF, LTB4, and P AF were present in high levels in closed-eye tears compared to open-ey e tears. Closed-eye tears were able to recruit neutrophils, with maxim al 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-regul ated the surface expression of IgA receptor, indicating that the GM-CS F in tears was functionally active. Up-regulation of cytokines and the lipid inflammatory mediator LTB4 during eye closure are noteworthy, a s each of these cytokines has an established role in initiation and am plification of the inflammatory response. IL-8 and LTB4 may act as pot ent chemoattractants and activators for PMNs, whereas IL-6 and GM-CSF potentiate the secretion and function of IgA and enhance neutrophil re sponsiveness to proinflammatory agonists.