Effects of 24h LPS-mediated inflammation on Submandibular Gland Function

Lipopolysaccharide can be used to mimic local and systemic infections in experimental studies. Objectives: To assess the effects of lipopolysaccharide on submandibular gland (SMG) secretion 24 hours after infusion. Methods: Male Wistar rats (250-300 g) were anaesthetized with ketamine & xylazine (75 & 15 mg/kg i.p., respectively). Lipopolysaccharide (Escherichia coli serotype O111:B4) was injected (50 μl, 0.5 mg/ml) in the right SMG duct from an intra-oral approach. The control left SMG duct was left unoperated. Twenty four hours later, under anaesthesia, both SMG ducts were cannulated and secretion was stimulated by intravenous infusion of autonomimetics. Salivas and salivary glands were collected, weighed and analyzed. All experiments were conducted under Home Office licence and local ethical committee approval. Results: Lipopolysaccharide infused SMG weight was increased (P < 0.001) compared to control contralateral glands (0.23 ± 0.02 g vs 0.19 ± 0.01 g, n = 6). Histologically, haematoxylin and eosin stained sections showed an extensive inflammatory cell infiltrate in lipopolysaccharide infused glands. Inducible nitric oxide synthase expression was detected by immunohistochemistry in the parenchyma of lipopolysaccharide treated glands. SMG salivary secretion from lipopolysaccharide infused glands was comparable to control glands (124 ± 16 μl/min/g vs 136 ± 17 μl/min/g, n = 5) with 12 μg/min/kg methacholine, but was increased (78 ± 22 μl/g/min vs 35 ± 8 μl/g/min, n = 6, P < 0.05) with a lower dose of methacholine (4 μg/min/kg). Conclusion: 24 hours following a single infusion of lipopolysaccharide there is a greatly increased infiltration of inflammatory cells in the gland parenchyma, compared to that previously observed 3h following lipopolysaccharide infusion. Nevertheless, salivary secretion is still not reduced and remains increased in response to a low dose of methacholine. It is concluded that lipopolysaccharide induced sialadenitis does not cause salivary hypofunction. Acknowledgement: this work was supported by the Welcome Trust.