Abstract
BackgroundRheumatoid 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.MethodsIn 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.ResultsFollowing LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-α 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 μM. 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.ConclusionThese data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.
Highlights
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
A lipid-rich extract of Perna was shown to prevent the development of adjuvant-induced polyarthritis and collagen-induced auto-allergic arthritis in rats [16]
We demonstrate that in vitro treatment with extracts derived from Perna canaliculus inhibited the production of several proinflammatory cytokines by a monocytic cell line
Summary
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. Amino acids, and natural compounds have shown a significant ability to regulate immune responses, including interferon-γ (IFN-γ) [1,2,3,4], steroids [5,6,7], DMG [8,9,10,11] and extracts from the New Zealand green-lipped mussel, Perna [12,13]. A New Zealand green-lipped mussel preparation, has demonstrated strong anti-inflammatory properties and was shown to be as efficient as non-steroidal antiinflammatory drugs (NSAIDs) at reducing inflammation in rats with carrageenan-induced footpad edema [12]. A lipid-rich extract of Perna was shown to prevent the development of adjuvant-induced polyarthritis and collagen-induced auto-allergic arthritis in rats [16] This therapeutic effect was associated with the inhibition of prostaglandins and leukotriene B4 biosynthesis. Perna contains the histamine blocker lysolecithin that likely contributes to its anti-inflammatory properties [17]
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