Effects of Ductal Lipopolysaccharide Infusion on Submandibular Gland Function

Background: The authors have shown previously that 24 hours after duct ligation of the rat submandibular gland (SMG) there is a dramatic reduction in salivary flow accompanied by an inflammatory response. Objectives: Evaluate the acute effects of an intra-ductal bolus infusion of lipopolysaccharide (LPS) on rat SMG secretory function. Methods: Male Wistar rats (225-285 g) were anaesthetized with pentobarbitone (50 mg/kg i.p.) and chloralose (80 mg/kg i.v.). LPS (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 received the same volume of sterile saline. Three hours later, still under anaesthesia, both SMG ducts were cannulated and salivary secretion was stimulated by an infusion of autonomimetics into the femoral vein. Salivas and salivary glands were collected, weighed and analyzed. All experiments were conducted under Home Office licence with appropriate local ethical committee approval. Results: Mean right SMG weight was increased (p<0.05) compared to control contralateral glands (R vs L, 0.31±0.02 g 0.24±0.01 g, n=4). Salivary flow rate evoked by methacholine (12 µg.min-1.kg-1) from the right LPS challenged glands (116±17 µl.min-1.g-1) was similar to the control gland (106±12 µl.min-1.g-1). When a lower methacholine dose (4 µg.min-1.kg-1) was used, the right SMG secreted more saliva (43±2.44 µl.g-1.min-1, p<0.05) than the control glands (22±2.1 µl.g-1.min-1). Microscopy of haematoxylin and eosin stained sections showed a great number of polymorphonuclear inflammatory cells in the right gland, but not in the control gland. Conclusions: After three hours of a local LPS challenge, the SMG secretory process is not affected. Interestingly, with a small dose of methacholine, SMG secretion is increased. Acknowledgement: this work was supported by the Welcome Trust.