Impact of gender on exocrine gland inflammation in mouse models of Sjogren's syndrome

Sjogren's syndrome is a complex autoimmune disorder, that occurs almost exc lusively in females, induces extensive lymphocyte accumulation in lacrimal and salivary glands, and represents one of the leading causes of dry eye an d mouth in the world. The purpose of this study was to determine whether th e profound, gender-related differences observed in the magnitude of exocrin e gland inflammation in Sjogren's syndrome may also be found in tissues of mouse models of this disorder. Lacrimal and submandibular glands were obtai ned from adult MRL/lpr, MRL+/+ (MRL+), NZB/NZW F1 (F1), C3H/lpr, C3H/gld (g ld), C57BL/6-lpr/lpr [B6/lpr; with (bcl-2(+)/lpr) or without (bcl-2-/lpr) b cl-2 transgene insertion] and nonobese diabetic (NOD) mice after the onset of autoimmune disease, and processed for microscopy and image analysis. Our results showed that: (1) the extent of inflammation was significantly grea ter in lacrimal glands of female MRL/lpr, MRL+, F1, C3H/lpr and gld mice, a nd salivary glands of female MRL+, F1 and gld mice, relative to those of ma les: (2) the severity of inflammation in NOD mice showed a tissue-specific pattern: inflammation was far worse in lacrimal glands of males, whereas im mune pathology was far greater in salivary tissues in females; and (3) no g ender-related variations were present in the degree of inflammation in lacr imal glands of bcl-2+/lpr and bcl-2-/lpr mice or in submandibular tissues o f MRL/lpr, C3H/lpr, bcl-2(+)/lpr Emd bcl-2-/lpr mice. Our findings demonstr ate that gender-, strain- and tissue-related differences exist in the exten t of inflammation in several mouse models of Sjogren's syndrome. (C) 1999 A cademic Press.