Abstract
Platelet activating factor (PAF), a potent inflammatory mediator, is a biologically active phospholipid. Recent studies have shown that PAF may play an important role in the pathogenesis of inflammation. WEB 2170 BS has been shown to be a PAF antagonist both in vitro and in vivo. Nitric oxide (NO) is present in the mammalian nasal airways and originates primarily from the paranasal sinuses. Measurement of NO is thought to be a surrogate marker of upper airway inflammation. In this study, the anti-inflammatory effects of WEB 2170 BS were investigated in a rabbit model of sinusitis. To induce experimental sinusitis, we applied killed Staphylococcus aureus percutaneously to the maxillary sinus of rabbits without occlusion of the natural ostium. Either WEB 2170 BS solution or placebo was administered intraperitoneally 2 hours before sinus inoculation, and this procedure was repeated twice daily for 4 days. The outcome of the treatment was determined by the measurement of NO metabolite levels and NO synthase activity in the samples of sinus mucosa and by histopathologic evaluation of sinus mucosa. The pathological grading was determined by the number of inflammatory cells found in the sinus mucosa. The levels of NO metabolites and NO synthase activity were found to be significantly lower in the WEB 2170 BS-treated group than in the control group. Histopathologic analysis of the sinus mucosa indicated decreased inflammation in the treated group as compared to the controls. These results demonstrate that WEB 2170 BS may produce significant anti-inflammatory effects in this model of sinusitis.
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