Ingested (oral) tocilizumab inhibits EAE

被引:13
作者
Brod, Staley A. [1 ]
Bauer, Victoria L. [1 ]
机构
[1] Univ Texas Houston, Hlth Sci Ctr, Dept Neurol, Houston, TX 77030 USA
关键词
Oral proteins; Tocilizumab; Antibody; EAE; Adoptive transfer; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; DENDRITIC CELLS; RHEUMATOID-ARTHRITIS; RECEPTOR ANTIBODY; PERIPHERAL-BLOOD;
D O I
10.1016/j.cyto.2014.04.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Background: Blocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Objective: We examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemre (R)), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration. Design/method: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TCZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or TCZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. Results: Ingested (oral) TCZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TCZ fed donors protected against actively induced disease and decreased inflammation. There was a decrease in IL-6 in actively treated spleen, decrease in TNF-alpha, Th1-like cytokine IL-12 and increase in Th2-like cytokine IL-10 in active fed and adoptively treated recipients. Conclusions: Ingested (orally administered) TCZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like cytokines and increase Th2-like anti-inflammatory cytokines. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:86 / 93
页数:8
相关论文
共 57 条
[1]
ADERKA D, 1989, J IMMUNOL, V143, P3517
[2]
ALVORD EC, 1965, ANN NY ACAD SCI, V122, P333
[3]
Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab [J].
Araki, Manabu ;
Aranami, Toshimasa ;
Matsuoka, Takako ;
Nakamura, Masakazu ;
Miyake, Sachiko ;
Yamamura, Takashi .
MODERN RHEUMATOLOGY, 2013, 23 (04) :827-831
[4]
IL-12 dependent/IFN-γ independent expression of CCR5 by myelin-reactive T cells correlates with encephalitogenicity [J].
Bagaeva, LV ;
Williams, LP ;
Segal, BM .
JOURNAL OF NEUROIMMUNOLOGY, 2003, 137 (1-2) :109-116
[5]
The gp130-stimulating designer cytokine hyper-IL-6 promotes the expansion of human hematopoietic progenitor cells capable to differentiate into functional dendritic cells [J].
Bernhard, H ;
Lohmann, M ;
Batten, WY ;
Metzger, J ;
Löhr, HF ;
Peschel, C ;
zum Büschenfelde, KHM ;
Rose-John, S .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (04) :365-372
[6]
Increased and long-term generation of dendritic cells with reduced function from IL-6-deficient bone marrow [J].
Bleier, JI ;
Pillarisetty, VG ;
Shah, AB ;
DeMatteo, RP .
JOURNAL OF IMMUNOLOGY, 2004, 172 (12) :7408-7416
[7]
Ingested (oral) ACTH inhibits EAE [J].
Brad, Staley A. ;
Hood, Zachary M. .
JOURNAL OF NEUROIMMUNOLOGY, 2011, 232 (1-2) :131-135
[8]
SUPPRESSION OF RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN THE SJL/J MOUSE BY ORAL-ADMINISTRATION OF TYPE-I INTERFERONS [J].
BROD, SA ;
BURNS, DK .
NEUROLOGY, 1994, 44 (06) :1144-1148
[9]
MODIFICATION OF ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN THE LEWIS RAT BY ORAL-ADMINISTRATION OF TYPE-1 INTERFERONS [J].
BROD, SA ;
SCOTT, M ;
BURNS, DK ;
PHILLIPS, JT .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1995, 15 (02) :115-122
[10]
Ingested (oral) alpha-MSH inhibits acute EAE [J].
Brod, Staley A. ;
Hood, Zachary M. .
JOURNAL OF NEUROIMMUNOLOGY, 2008, 193 (1-2) :106-112