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 journalArticlepeer-review

60 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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