Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits

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

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Intravitreal injection of lipopolysaccharide (LPS) induces leukocyte infiltration and protein leakage into the aqueous humor. In the present study, we investigated the role of IL-8 and MCP-1 and regulation of these chemokines by TNFα and IL-1 in LPS-induced uveitis in rabbits. After intravitreal injection of LPS, generation of IL-8 in the aqueous humor showed a biphasic pattern with the first peak at 12 hr and the second one at 24 hr, while MCP-1 was produced in a monophasic pattern and peaked at 24 hr. Immunohistochemistry showed that ciliary epithelial cells and infiltrating leukocytes were the producing cells of IL-8 and MCP-1. Administration of anti-IL-8 IgG suppressed by 66% the peak levels of LPS-induced aqueous neutrophil counts at 24 hr but did not suppress aqueous mononuclear cell counts or protein levels. Anti-MCP-1 IgG inhibited aqueous mononuclear cell counts by 41% and protein levels by 28%, but did not inhibit aqueous neutrophil counts. The levels of LPS-induced aqueous IL-8 and MCP-1 at 12 hr were inhibited by anti-TNFα mAb but not by an IL-1 receptor antagonist (IL- 1Ra), while concentrations of the two chemokines at 24 hr were inhibited by both anti-TNFα mAb and IL-1Ra. A combination of anti-TNFα mAb and rrIL-1Ra had an additive effect on the 24 hr-chemokine levels and inhibited up to 90% chemokine production. Taken together, our results show that IL-8 mediates neutrophil infiltration, while MCP-1 mediates mononuclear cell infiltration and protein leakage in LPS-induced uveitis in rabbits. Levels of aqueous IL8 and MCP-1 at 12 hr are regulated by TNFα, while levels at 24 hr are regulated by TNFα and IL-1.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalExperimental Eye Research
Volume68
Issue number3
DOIs
Publication statusPublished - Mar 1999
Externally publishedYes

Keywords

  • IL-1
  • IL-8
  • LPS
  • Leukocyte
  • MCP-1
  • TNFα
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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