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Parotid gland dysfunction in a murine model of acute graft versus host disease [aGVHD]
R M Nagler1, D Laufer, A Nagler
1Department of Oral and Maxillofacial Surgery, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Background:
The major salivary glands are target organs affected by acute graft versus host disease (aGVHD), resulting in severe xerostomia.
Methods:
We evaluated the function of the major salivary glands in an animal model of aGVHD (B10.S-->SJL/J). For the induction of aGVHD, SJL/J mice were sublethally irradiated with 900 cGy and injected with 2 x 10(7) splenocytes. The SJL/J mice that received 900 cGy total-body irradiation (TBI) and nonirradiated mice served as controls. Major salivary gland function was evaluated in vivo at the peak of aGVHD (proven both clinically and histologically). The volume, flow rate, salivation lag phase, and composition of secreted saliva were evaluated following intraperitoneal (IP) administration of pilocarpine (5 mg/kg) by cannulation of the main parotid excretory duct with polyethylene tubing.
Results:
We observed a significant decrease in the secreted saliva volume in the aGVHD mice, 12.4+/-1.7 microl/30 min, in comparison with 27.8+/-3.9 and 31.9+/-3.0 microl/30 min in the intact control and irradiated control mice, respectively (p < .001). Sialochemical evaluation revealed a significant decrease in total protein and a significant increase in potassium in the saliva secreted by the aGVHD mice, 2.6+/-0.4 mg/mL and 22.0+/-3.2 mEq/L, compared with 4.4+/-0.6 mg/mL and 14.9+/-2.0 mEq/L in the control mice, respectively (p < .05). A decrease in sodium concentration secreted by the aGVHD mice in comparison with the nonirradiated mice was statistically nonsignificant. Histopathologic evaluation of the parotid tissue of the aGVHD mice revealed massive infiltration of lymphocytes and almost total destruction of the normal parenchyma.
Conclusions:
We observed salivation hypofunction develop concomitantly with salivary tissue lymphocyte infiltration in an aGVHD animal model. We suggest that the lymphocytes and the secreted lymphokines are the cause of the salivary changes. This finding may provide an explanation for the severe oral changes and xerostomia observed in aGVHD patients.