Herbal medicine Gamgungtang down-regulates autoimmunity through induction of TH2 cytokine production by lymphocytes in experimental thyroiditis model

• Published in: Journal of ethnopharmacology 2007-02, Vol.109 (3), p.472-479
• Main Authors: Sa, Eun-Ho, Jin, Un-Ho, Kim, Dong-Soo, Kang, Bong-Seok, Ha, Ki-Tae, Kim, June-Ki, Park, Won-Hwan, Kim, Cheorl-Ho
• Format: Article
• Language: English
• Subjects: Angelica gigas; Angelicae radix ( Angelica gigas Nakai); Animals; autoimmune diseases; Autoimmunity - drug effects; Biological and medical sciences; biosynthesis; Black bean ( Glycine max L. Merr); chemical constituents of plants; Cnidii rhizoma ( Cnidium officinale Makino); Cnidium; Cnidium officinale; cytokines; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Cytotoxic T lymphocyte; ethnobotany; Experimental autoimmune thyroiditis; Female; Gamgungtang; General pharmacology; Glycine max; Glycyrrhiza Fissch; Glycyrrhiza uralensis; Glycyrrhizae radix ( Glyrrhiza uralensis Fischer; Herbal Medicine; herbal medicines; Immunomodulation; immunomodulators; In vivo animal model; lymphocytes; Medical sciences; medicinal plants; medicinal properties; Mice; Mice, Inbred Strains; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Extracts - pharmacology; rhizomes; RNA, Messenger - metabolism; TH1; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; TH2; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism; Thyroglobulin - pharmacology; thyroid diseases; Thyroiditis - drug therapy; Thyroiditis - immunology; Thyroiditis - metabolism; traditional medicine
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2006.08.017

The crude herbal formulation, Gamgungtang (GGT), has been shown to protect animals against a wide range of spontaneously developing or induced autoimmune diseases. We have previously reported that GGT shows marked down-regulation of several experimental autoimmune diseases. Although very effective at preventing thyroid infiltrates in mice immunized with mouse deglycosylated thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. In this study, in an effort to elucidate the mechanisms by which GGT suppresses EAT, and autoimmunity in general, we investigated the in vivo effects of this drug on the Th1/Th2 lymphocyte balance, which is important for the induction or inhibition of autoreactivity. Naive SJL/J mice were treated orally for 5 days with GGT (80 mg/(kg day)). Spleen cells were obtained at various time points during the treatment period and were stimulated in vitro with concanavalin A. Interleukins IL-4, IL-10 and IL-12, transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) cytokine production was evaluated at the protein levels of the cytokines in the medium and mRNA expressions. A significant upregulation of IL-4, IL-10 and TGF-β was observed following treatment with GGT, which peaked at day 5 (IL-10) or day 10 (IL-4). On the other hand, IL-12 and IFN-γ production were either unchanged or decreased. It seems therefore that GGT induces in vivo a shift towards Th2 lymphocytes which may be one of the mechanisms of down-regulation of the autoimmune reactivity in EAT. Our observations indicate that down-regulation of TH1 cytokines (especially IL-12) and enhancement of Th2 cytokine production may play an important role in the control of T-cell-mediated autoimmunity. These data may contribute to the design of new immunomodulating treatments for a group of autoimmune diseases.