Parotid salivary gland dysfunction in chronic graft-versus-host disease (cGVHD): a longitudinal study in a mouse model.

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like phenomenon resulting in morbidity and mortality following allogeneic bone marrow transplantation (BMT). Major salivary gland dysfunction and hyposalivation is one of the prevalent manifestations of cGVHD. We have used the B10.D2 to Balb/C cGVHD mice model in order to assess major salivary gland function in cGVHD, evaluating sialometric, sialochemical and histopathological parameters for almost 3 months. As cGVHD is a chronic debilitating disease it is of vast importance to evaluate these parameters on a prolonged longitudinal basis. We observed significant reduction in parotid salivary flow rate and disturbance in the salivary dynamic function in cGVHD mice in comparison to the normal and syngeneic transplanted controls. On days 18, 25, 46, 56 and 88 the mean flow rates of the cGVHD group were 37.4 +/- 4.4 microl/30 min, 40.5 +/- 4.6 microl/30 min, 32.5 +/- 2.3 microl/30 min, 22.2 +/- 3.2 microl/30 min and 14.8 +/- 3.8 microl/30 min, respectively, values which were lower than those of the syngeneic transplanted controls group by 42% (P < 0.04), 32% (P < 0.03), 44% (P < 0.01), 49% (P < 0.01) and 64% (P < 0.01), respectively. These changes in flow rates were paralleled by changes in the biochemical composition of the saliva. Moreover, the reduction in flow rates correlated with the degree of salivary gland destruction observed in the pathological slides. An inverse correlation was observed between the mean parotid salivary flow rate and the degree of fibrosis observed in the histopathological evaluation of the cGVHD mice (P < 0.01). Maximal flow rate 34.8 +/- 4.6 microl/30 min was observed when no fibrosis was observed while in mice with maximal fibrosis flow rates were minimal. This may point to the pathological mechanism leading to the major salivary gland dysfunction and hyposalivation observed in cGVHD. Thus, it may broaden our knowledge and provide the scientific background for designing better therapeutic strategies for this complication. Bone Marrow Transplantation (2000).