Human chorionic gonadotropin prevents Sjögren's syndrome-like exocrinopathy in mice.
OBJECTIVE
Results of recent studies suggest that human chorionic gonadotropin (HCG), a placental glycoprotein hormone required for the maintenance of pregnancy, may have immunomodulatory properties. Primary Sjögren's syndrome (SS), a chronic autoimmune disorder of unknown etiology, affects multiple exocrine glands including the salivary and lacrimal glands. The purpose of the present study was to determine whether HCG could prevent the development of salivary gland exocrinopathy in NOD mice, an experimental model of Sjögren's-like syndrome.


METHODS
Female NOD mice were treated with HCG from 6 weeks of age to 12 weeks of age. At 14 weeks, tissue samples were evaluated for inflammatory lesions and cytokine messenger RNA by real-time polymerase chain reaction. At 18 weeks, the salivary flow rate was measured.


RESULTS
Treatment with HCG resulted in a significant decrease in lymphocyte infiltration and parenchymal cell damage in the submandibular salivary glands. Messenger RNA levels of interferon-gamma, tumor necrosis factor alpha, interleukin-1beta, and interleukin-10, as well as inducible nitric oxide synthase and matrix metalloproteinase 9, were significantly decreased. Function studies revealed a marked increase in the salivary flow rate in HCG-treated mice compared with that in phosphate buffered saline-treated mice.


CONCLUSIONS
In NOD mice, HCG acts as an immune modulator and prevents the development of salivary gland exocrinopathy. These findings suggest that HCG, a naturally occurring reproductive hormone, may be useful in the treatment of Sjögren's syndrome and other human autoimmune diseases.
Li
Na
N
Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
Shigihara
Toshikatsu
T
Tzioufas
Athanasios G
AG
Notkins
Abner L
AL
Yoon
Ji-Won
JW
Jun
Hee-Sook
HS
D000818:Animals; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology; D012859:Sjogren's Syndrome / Q000517:prevention & control*
D006063:Chorionic Gonadotropin; D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma