A mouse model linking viral hepatitis and salivary gland dysfunction.
OBJECTIVE
Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis.


METHODS
BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage.


RESULTS
Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected.


CONCLUSIONS
Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.
Kasman
L M
LM
Department of Microbiology and Immunology, Medical University of South Carolina, BSB-201, PO Box 250504, 173 Ashley Ave, Charleston, SC 29403, USA. kasmanl@musc.edu
London
L L
LL
London
S D
SD
Pilgrim
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000150:complications* / Q000821:virology; D006566:Herpesviridae Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018146:Muromegalovirus / Q000472:pathogenicity*; D012472:Salivation / Q000502:physiology; D018709:Statistics, Nonparametric; D014987:Xerostomia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000821:virology
D051402:Aquaporin 5