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 trans plantation (BMT), Major salivary gland dysfunction and hyposalivation is on e 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 cGV HD, evaluating sialometric, sialochemical and histopathological parameters for almost 3 months. As cGVHD is a chronic debilitating disease it is of va st importance to evaluate these parameters on a prolonged longitudinal basi s. We observed significant reduction in parotid salivary flow rate and dist urbance 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 mu l/30 min, 40.5 +/- 4.6 mu l/30 min, 32.5 +/- 2.3 mu l/30 min, 22.2 +/- 3.2 mu l/30 min and 14.8 +/- 3.8 mu l/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. Thes e changes in flow rates were paralleled by changes in the biochemical compo sition of the saliva. Moreover, the reduction in flow rates correlated with the degree of salivary gland destruction observed in the pathological slid es. An inverse correlation was observed between the mean parotid salivary f low rate and the degree of fibrosis observed in the histopathological evalu ation of the cGVHD mice (P ( 0.01). Maximal how rate 34.8 +/- 4.6 mu l/30 m in was observed when no fibrosis was observed while in mice with maximal fi brosis flow rates were minimal. This may point to the pathological mechanis m leading to the major salivary gland dysfunction and hyposalivation observ ed in cGVHD. Thus, it may broaden our knowledge and provide the scientific background for designing better therapeutic strategies for this complicatio n.