INCREASED INTERLEUKIN-1 ACTIVITY IN THE INJURED VITAMIN-A-DEFICIENT CORNEA

Injury to a vitamin A-deficient cornea leads to severe acute inflammat ion often culminating in ulceration. We report on possible regulatory mechanisms involved in the pathogenesis of corneal inflammation in vit amin A deficiency. Thymocyte comitogenic assay and interleukin (IL)-6 induction in corneal fibroblasts have shown that thermally injured and mechanically abraded vitamin A-deficient rat corneas produce much hig her levels of an IL-1-like factor as compared with uninjured or injure d normal control corneas. This was confirmed by antibody capture enzym e immunoassays, which detected high levels of IL-1alpha and IL-1beta i n injured vitamin A-deficient corneas. To our knowledge this is the fi rst report describing the induction of IL-1 in the vitamin A-deficient cornea by thermal and mechanical injuries. When mechanically injured corneas were screened for chemotactic activity, they were found to con tain significantly higher levels of a chemoattractant as compared with similarly injured, normal control corneas. Chemotactic activity [expr essed as a percentage of a known chemotactic tripeptide, formyl-methio nyl-leucyl-phenylalanine (fMLP), found in medium harvested from vitami n A-deficient corneas] averaged 58.8 +/- 8.9% (SEM) as compared with 1 2.6 +/- 5.4% in medium conditioned by normal corneas. Checkerboard ana lysis confirmed that the activity in vitamin A-deficient cornea condit ioned medium was chemotactic and not chemokinetic. These results demon strate a correlation between IL-1 levels and severity of inflammation in the injured vitamin A-deficient rat cornea.