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Azithromycin reduces inflammation in a rat model of acute conjunctivitis
Patricia Fernandez-Robredo1, Sergio Recalde, Maite Moreno-Orduña
1Experimental Ophthalmology Laboratory, Universidad de Navarra, Pamplona Navarra, Spain. pfrobredo@unav.es
Purpose:
Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated.
Methods:
Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0).
Results:
Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05).
Conclusions:
These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.
Insights
Azithromycin significantly reduced clinical signs of acute conjunctivitis in rats. This macrolide antibiotic decreased inflammatory markers, suggesting its therapeutic potential for eye inflammation.
Area of Science:
- Ophthalmology
- Pharmacology
- Immunology
Background:
- Macrolide antibiotics possess anti-inflammatory properties beyond their antimicrobial effects.
- The precise mechanisms underlying the anti-inflammatory actions of macrolides remain incompletely understood.
Purpose of the Study:
- To investigate the anti-inflammatory effects of azithromycin.
- To elucidate the impact of azithromycin on inflammatory molecules in a lipopolysaccharide-induced rat conjunctivitis model.
Main Methods:
- Topical ocular azithromycin or vehicle was administered to Wistar rats prior to lipopolysaccharide injection.
- Clinical signs, mucus secretion, gene expression (interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, MMP-2, MMP-9), protein expression (NF-κB), and MMP-2 activity were assessed.
- Histological and immunofluorescence analyses were performed on conjunctival tissues.
Main Results:
- Azithromycin treatment significantly reduced clinical signs of conjunctivitis, including edema and redness (p<0.05).
- Key inflammatory markers such as interleukin-6, nuclear factor-kappa B protein, and MMP-2 activity were significantly decreased in azithromycin-treated rats (p<0.05).
- Mucus secretion and macrophage infiltration in conjunctival tissue were also significantly reduced by azithromycin (p<0.05).
Conclusions:
- Azithromycin administration effectively ameliorates the inflammatory effects in an experimental model of acute conjunctivitis.
- These findings highlight azithromycin's potential as a therapeutic agent for inflammatory eye conditions.
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