Ethyl pyruvate ameliorates endotoxin-induced corneal inflammation.

Abstract

PURPOSE:

The purpose of this study was to evaluate the anti-inflammatory effect of ethyl pyruvate (EP) in a mouse model of lipopolysaccharide (LPS)-induced corneal inflammation.

METHODS:

LPS was injected intrastromally into the corneas of C57BL/6 mice followed by treatment with a solution of 2.5% EP in 0.2% hydroxypropyl methylcellulose (HPMC) every 90 minutes during the course of 12 hours. Prednisolone acetate 1% solution (PRED FORTE) was used as a positive control. Mice were sacrificed after 3 days, and corneas were examined by in vivo confocal microscopy and analyzed for infiltrated cells by flow cytometry. Gr-1, TNF-α, and pNF-κB-p65 were detected immunohistochemically, and TNF-α, IL-6, and IL-1β levels were quantified by ELISA.

RESULTS:

LPS-induced haze in mice corneas was decreased by 2-fold upon EP treatment; however, it was not changed upon PRED FORTE treatment. Flow cytometry and immunohistochemistry showed infiltration of leukocytes in the LPS-treated corneas; among the infiltrated cells, neutrophils (Gr-1+ and CD11b+) and macrophages (F4/80+ and CD11b+) were 3403.4- and 4.5-fold higher in number, respectively, than in vehicle-treated control corneas. EP or PRED FORTE treatment of LPS-injected corneas decreased the number of neutrophils 7.5- and 7.2-fold and macrophages by 5.6- and 3.5-fold, respectively. Both EP and PRED FORTE decreased TNF-α and IL-6 expression considerably, and to a lesser extent IL-1β expression, in the LPS-treated corneas.

CONCLUSIONS:

The present study demonstrated that EP reduces LPS-induced inflammation in the cornea and thus may have a potential therapeutic application in the inhibition of corneal inflammation.

• Authors: Divya Gupta, Yiqin Du, Jordan Piluek, Adam M Jakub, Kristine Ann Buela, Akshar Abbott, Joel S Schuman, Nirmala SundarRaj
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 10 Pg. 6589-99 (Sep 25 2012) ISSN: 1552-5783 [Electronic] United States
• PMID: 22918642 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Gr-1 protein, mouse
• Lipopolysaccharides
• Ophthalmic Solutions
• Pyruvates
• Receptors, Chemokine
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• ethyl pyruvate

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cell Migration Assays, Leukocyte
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Fluorescent Antibody Technique, Indirect
• Keratitis (chemically induced, metabolism, prevention & control)
• Leukocytes (physiology)
• Lipopolysaccharides (toxicity)
• Mice
• Mice, Inbred C57BL
• Microscopy, Confocal
• Ophthalmic Solutions (therapeutic use)
• Pyruvates (therapeutic use)
• Receptors, Chemokine (metabolism)
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)