Increased interleukin-1 activity in the injured vitamin A-deficient cornea.
Injury to a vitamin A-deficient cornea leads to severe acute inflammation often culminating in ulceration. We report on possible regulatory mechanisms involved in the pathogenesis of corneal inflammation in vitamin 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 higher levels of an IL-1-like factor as compared with uninjured or injured, normal control corneas. This was confirmed by antibody capture enzyme immunoassay, which detected high levels of IL-1 alpha and IL-1 beta in injured vitamin A-deficient corneas. To our knowledge this is the first 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 contain significantly higher levels of a chemoattractant as compared with similarly injured, normal control corneas. Chemotactic activity [expressed as a percentage of a known chemotactic tripeptide, formyl-methionyl-leucyl-phenylalanine (fMLP), found in medium harvested from vitamin A-deficient corneas] averaged 58.8 +/- 8.9% (SEM) as compared with 12.6 +/- 5.4% in medium conditioned by normal corneas. Checkerboard analysis confirmed that the activity in vitamin A-deficient cornea conditioned medium was chemotactic and not chemokinetic. These results demonstrate a correlation between IL-1 levels and severity of inflammation in the injured vitamin A-deficient rat cornea.
Shams
N B
NB
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114.
Reddy
C V
CV
Watanabe
K
K
Elgebaly
S A
SA
Hanninen
L A
LA
Kenyon
K R
KR
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003315:Cornea / Q000276:immunology* / Q000473:pathology; D003320:Corneal Ulcer / Q000276:immunology / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014802:Vitamin A Deficiency / Q000276:immunology* / Q000473:pathology
D007375:Interleukin-1; D015850:Interleukin-6