Suppression of streptococcal cell wall-induced arthritis by human chorionic gonadotropin.
OBJECTIVE
To determine whether human chorionic gonadotropin (HCG) contributes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoid arthritis, during pregnancy.


METHODS
Administration of HCG was initiated 2 days prior to an arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and the development and severity of SCW-induced arthritis was monitored. Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels, were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine messenger RNA expression in joint tissue were compared between treated and untreated arthritic animals.


RESULTS
Systemic administration of HCG resulted in a dose-dependent reduction in the clinical arthritis index. Consistent with the amelioration of clinical symptoms, HCG significantly reduced the inflammatory cell infiltration, pannus formation, and bone and cartilage degradation. Mechanistically, HCG therapy was associated with suppression of the overzealous production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1beta, which contribute to synovial pathology in animals with SCW-induced arthritis. Circulating nitric oxide and the amount of iNOS protein were also reduced. Furthermore, circulating transforming growth factor beta levels were elevated by the HCG, all of which suggest monocytes/macrophages as a potential target.


CONCLUSIONS
These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory mediators.
Song
X Y
XY
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
Zeng
L
L
Jin
W
W
Pilo
C M
CM
Frank
M E
ME
Wahl
S M
SM
D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy*; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011917:Rats, Inbred Lew; D013290:Streptococcal Infections; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D015850:Interleukin-6; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C496319:NOS2 protein, human; C496318:Nos2 protein, rat