Ethyl pyruvate ameliorates endotoxin-induced corneal inflammation

Invest Ophthalmol Vis Sci. 2012 Sep 25;53(10):6589-99. doi: 10.1167/iovs.11-9266.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Keratitis / metabolism
  • Keratitis / 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


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