Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus.
BACKGROUND
Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses.


METHODS
In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes in vitro with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent in vivo experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators.


RESULTS
Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-alpha and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001-1 microM. We also demonstrate that in vitro neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner.


CONCLUSIONS
These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.
Lawson
Brian R
BR
Department of Biological Sciences, Clemson University, Clemson, SC, USA. blawson@scripps.edu
Belkowski
Stanley M
SM
Whitesides
John F
JF
Davis
Paul
P
Lawson
John W
JW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001842:Bone and Bones / Q000187:drug effects* / Q000276:immunology; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D049883:Perna; D051381:Rats; D012521:Sarcosine / Q000031:analogs & derivatives*
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; C025138:dimethylglycine; D003094:Collagen; D012521:Sarcosine