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

Exp Eye Res. 1999 Mar;68(3):333-40. doi: 10.1006/exer.1998.0618.


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 TNFalpha 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-TNFalpha 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-TNFalpha mAb and IL-1Ra. A combination of anti-TNFalpha 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 IL-8 and MCP-1 at 12 hr are regulated by TNFalpha, while levels at 24 hr are regulated by TNFalpha and IL-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Aqueous Humor / immunology*
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / immunology
  • Chemokines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoglobulin G / immunology
  • Immunohistochemistry
  • Interleukin-1 / immunology
  • Interleukin-8 / analysis
  • Interleukin-8 / immunology
  • Leukocytes / immunology
  • Lipopolysaccharides
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / immunology
  • Uveitis / immunology*
  • Uveitis / microbiology


  • Antibodies, Monoclonal
  • Chemokine CCL2
  • Chemokines
  • Immunoglobulin G
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha