β2-adrenoceptor blocker ICI118551 attenuates Pseudomonas aeruginosa
corneal infection in mice
Abstract
Purpose: Our previous studies have confirmed that the catecholamine
norepinephrine (NE) promoted the corneal infection and progression of
Pseudomonas aeruginosa (P. aeruginosa) keratitis. Here we explored the
effects of adrenoceptor (AR) blockers on the severity of P. aeruginosa
keratitis in mice. Methods: A total of 630 C57BL/6 mice were used and
ocularly inoculated with P. aeruginosa (ATCC 19660). Six AR blockers
were topically administrated 6 h before or combined with Tobrex 12 h
after bacterial inoculation. Clinical scores, neutrophil infiltration
and neutrophil extracellular traps (NETs), proinflammatory factors and
bacterial virulence factors expression, bacterial load and biofilm
formation were evaluated in vivo. The growth inhibitory and bactericidal
activity of ICI118551 was measured in vitro. Results: Among various
blockers, the selective β2-AR blocker ICI118551 showed the most
significant improvement in disease severity. Prophylactic administration
of ICI118551 attenuated the clinical scores, neutrophil infiltration,
NETs formation, proinflammatory factors expression of infected corneas,
accompanied with the reduction of bacterial load, virulence factors
expression, and biofilm formation. When adjunctive treatment with
Tobrex, ICI118551 exhibited apparent therapeutic effects with the
reduced severity after 12 h of bacterial inoculation. Moreover,
ICI118551 inhibited bacterial growth and possessed bactericidal activity
in vitro. In addition, ICI118551 had no significant influence on ocular
barrier function and intraocular pressure. Conclusions: The selective
β2-AR blocker ICI118551 attenuated the severity of P. aeruginosa
keratitis in mice, which may represent the potential prophylactic and
therapeutic approach to control the P. aeruginosa corneal infection.