Effects of exogenous interleukin-6 during Pseudomonas aeruginosa corneal infection

Abstract

Lack of interleukin-6 (IL-6) during Pseudomonas aeruginosa corneal infection leads to more severe disease with changes in neutrophil recruitment. Exogenous IL-6 leads to increased efficiency of neutrophil recruitment and reduced bacterial loads in corneal infection in both IL-6 gene knockout and wild-type mice. This may be mediated by IL-6 increasing the production of corneal macrophage inflammatory protein 2 and intercellular cell adhesion molecule 1. We conclude that effective recruitment of neutrophils into the cornea is dependent on the production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.

FIG. 1

Histopathology of corneas from IL-6 gko and wild-type mice 12 h after challenge with P. aeruginosa. All sections are stained with hematoxylin and eosin. Magnification of all sections, ×176. (A) Cornea of IL-6 gko mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of PBS. The central cornea contains only the occasional inflammatory cell. There are numerous PMN in the anterior chamber. (B) Cornea of wild-type mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of PBS. The cornea contains infiltrating inflammatory cells, predominantly PMN. (C) Cornea of IL-6 gko mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of IL-6. The central cornea contains inflammatory cells, predominantly PMN. There are numerous PMN in the anterior chamber. (D) Cornea of wild-type mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of IL-6. The infiltrating inflammatory cells in the cornea are more numerous than in panel B.

FIG. 2

Numbers of viable bacteria and PMN and cytokine production in the eyes of IL-6 gko and wild-type mice 12 h after challenge with P. aeruginosa after treatment with either PBS or IL-6. Histograms represent the mean of observation from the experiment, and vertical bars indicate standard errors. ∗, P < 0.05. (A) Viable bacteria; (B) PMN; (C) IL-6; (D) MIP-2; (E) KC; (F) IFN-γ; (G) TNF-α.

FIG. 3

ICAM-1 expression in the corneas of wild-type and IL-6 gko mice 12 h after challenge with P. aeruginosa. Magnification of sections, ×200. (A) Cornea of IL-6 gko mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of PBS. (B) Cornea of wild-type mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of PBS. (C) Cornea of IL-6 gko mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of IL-6. (D) Cornea of wild-type mouse 12 h after challenge with P. aeruginosa after subconjunctival injection of IL-6.