Involvement of TNFα, IL-1β and IL-1 receptor antagonist in LPS- induced rabbit uveitis

Jun Song Mo, Akihiro Matsukawa, Susumu Ohkawara, Masaru Yoshinaga

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

The objective of the study was to investigate involvement of TNFα, IL- 1β and IL-1 receptor antagonist (IL-1Ra) in lipopolysaccharide (LPS)- induced uveitis. Intravitreal injection of LPS (100 ng) to rabbits induced a massive leukocyte infiltration and protein leakage into the aqueous humor. Aqueous leukocyte counts and protein levels reached a peak 24 hr after this injection. The peak concentrations of aqueous TNFα (230 ± 37 pg ml-1, at 9 hr) and IL-1β (185 ± 80 pg ml-1, at 18 hr) preceded peak levels of aqueous leukocyte counts and protein levels. In contrast, the levels of aqueous IL-1Ra peaked at 48 hr (12239 ± 1964 pg ml-1) and a fairly high concentration of IL-1Ra remained when the inflammatory reactions subsided. Immunohistochemistry and leukocyte-depletion studies showed that infiltrating leukocytes were the major cellular sources of aqueous TNFα, IL-1β and IL- 1Ra. Intravitreal injection of homologous TNFα (0.1-1.5 μg) or IL-1β (0.5- 5 ng) reproduced a rapid leukocyte infiltration and protein leakage. Administration of anti-TNFα mAb (10 μg) suppressed the number of LPS- induced infiltrating neutrophils by 50%, mononuclear cells by 58%, and protein leakage by 42%. Administration of rabbit IL-1Ra (10 μg) also suppressed neutrophil influx by 78%, however, neither mononuclear cell influx nor protein leakage was inhibited by rabbit IL-1Ra. Co-administration of the two inhibitors enhanced inhibition of neutrophil infiltration to 88%, and protein leakage to 64%. We conclude that TNFα and IL-1β are the principal mediators of LPS-induced uveitis. Our observations also suggest that endogenous IL-1Ra may down-regulate inflammatory reactions.

Original languageEnglish
Pages (from-to)547-557
Number of pages11
JournalExperimental Eye Research
Volume66
Issue number5
DOIs
Publication statusPublished - May 1998
Externally publishedYes

Keywords

  • IL-1
  • IL-1 receptor antagonist
  • LPS
  • TNFα
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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