GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells.
This study investigated whether GV1001 may be useful for treating rheumatoid arthritis (RA). Two collagen-induced arthritis (CIA) experiments showed that therapeutic, but not preventive, GV1001 treatment reduced the severity of joint inflammation in CIA. The third CIA experiment indicated that, compared to vehicle treatment, therapeutic GV1001 treatment was associated with a significantly smaller area under the curve for the overall clinical joint score over the 98day observation period (p<0.05). GV1001 treatment was also associated with lower Day 98 serum IL-6 levels (p<0.01) and histological joint scores (p<0.05). Moreover, splenocytes harvested from the GV1001-treated mice exhibited lower basal and collagen-stimulated production of IFN-γ and IL-6 on Days 49 and 98 than the splenocytes from vehicle-treated mice. The fourth and fifth experiments indicated that earlier treatment resulted in a better response. In addition, human (THP-1) and murine (RAW 264.7) macrophages and fibroblast-like synoviocytes (FLS) from RA patients were used for in vitro analyses. GV1001 treatment of lipopolysaccharide-stimulated macrophages derived from THP-1 and RAW 264.7 monocytes significantly reduced TNF-α and IL-6 secretion (THP-1: all p<0.05; RAW 264.7: all p<0.01). However, GV1001 treatment did not affect IL-6 expression in TNFα-stimulated RA FLS. GV1001 reduced the clinical joint scores, serum IL-6 levels, and histological joint scores of mice with CIA. In addition, GV1001 lowered the collagen-stimulated IFN-γ and IL-6 production of murine T-cells and reduced the TNF-α and IL-6 production of macrophages in vitro. Thus, GV1001 may ameliorate joint inflammation by modifying T-cell reactions to the triggering autoantigen and by reducing macrophage cytokine production.
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Electronic address: iachoi@cbnu.ac.kr.
In Ah
IA
Choi
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
Ji Yong
JY
Choi
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
Sundo
S
Jung
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
Fathihah
F
Basri
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea. Electronic address: sehopark@korea.ac.kr.
Seho
S
Park
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Electronic address: elee@snu.ac.kr.
Eun Young
EY
Lee
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D003094:Collagen / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000276:immunology*; D000067996:RAW 264.7 Cells; D000070918:Synoviocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology*
D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; D007371:Interferon-gamma; D003094:Collagen; C514987:GV1001 peptide; D019098:Telomerase
Rheumatoid arthritis; T-cell