Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody: Use of rheumatoid arthritis tissue implants in the SCID mouse model

Matsuno, Hiroaki; Sawai, Takashi; Nezuka, T.; Uzuki, Miwa; Tsuji, Haruo; Nishimoto, Norihiro; Yoshizaki, Kazuyuki

doi:10.1002/1529-0131(199811)41:11<2014::aid-art17>3.0.co;2-t

Cited by 44 publications

(21 citation statements)

References 38 publications

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“…For example, infliximab is a mAb to TNF-␣ and has inhibitory effects on joint destruction (4, 38 -41). Also, the anti-IL-6 receptor mAb tocilizumab has been reported to exert antiproliferative effects on the synovial membrane, reduce inflammatory mononuclear cell infiltration, and inhibit the differentiation of osteoclasts in RA (5,(42)(43)(44). In vitro studies have demonstrated increased AIF-1 expression by macrophage cell lines in response to IFN-␥, whereas AIF-1 gene transfected mouse macrophage cell lines exhibit increased production of IL-6, IL-10, and IL-12 p40 following LPS stimulation (45).…”

Section: Discussionmentioning

confidence: 99%

A Critical Role for Allograft Inflammatory Factor-1 in the Pathogenesis of Rheumatoid Arthritis

Kimura

Kawahito

Obayashi³

et al. 2007

The Journal of Immunology

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Rheumatoid arthritis (RA) is characterized by massive synovial proliferation, angiogenesis, subintimal infiltration of inflammatory cells and the production of cytokines such as TNF-α and IL-6. Allograft inflammatory factor-1 (AIF-1) has been identified in chronic rejection of rat cardiac allografts as well as tissue inflammation in various autoimmune diseases. AIF-1 is thought to play an important role in chronic immune inflammatory processes, especially those involving macrophages. In the current work, we examined the expression of AIF-1 in synovial tissues and measured AIF-1 in synovial fluid (SF) derived from patients with either RA or osteoarthritis (OA). We also examined the proliferation of synovial cells and induction of IL-6 following AIF-1 stimulation. Immunohistochemical staining showed that AIF-1 was strongly expressed in infiltrating mononuclear cells and synovial fibroblasts in RA compared with OA. Western blot analysis and semiquantitative RT-PCR analysis demonstrated that synovial expression of AIF-1 in RA was significantly greater than the expression in OA. AIF-1 induced the proliferation of cultured synovial cells in a dose-dependent manner and increased the IL-6 production of synovial fibroblasts and PBMC. The levels of AIF-1 protein were higher in synovial fluid from patients with RA compared with patients with OA (p < 0.05). Furthermore, the concentration of AIF-1 significantly correlated with the IL-6 concentration (r = 0.618, p < 0.01). These findings suggest that AIF-1 is closely associated with the pathogenesis of RA and is a novel member of the cytokine network involved in the immunological processes underlying RA.

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Section: Discussionmentioning

confidence: 99%

A Critical Role for Allograft Inflammatory Factor-1 in the Pathogenesis of Rheumatoid Arthritis

Kimura

Kawahito

Obayashi³

et al. 2007

The Journal of Immunology

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“…MIF production is induced by low, but not high, doses of glucocorticoids, as well as by mild stress (31). MIF overrides glucocorticoidinduced suppression of gene expression of proinflammatory cytokines, including tumor necrosis factor-␣, IL-1␤, IL-6, and IL-8 (31,32), all of which have been associated with increases in inflammatory disease activity (33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Repeated, but not acute, stress suppresses inflammatory plasma extravasation

Strausbaugh

Dallman

Levine

1999

Proc. Natl. Acad. Sci. U.S.A.

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Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases. There is considerable evidence that stress can exacerbate a number of chronic inflammatory diseases. For example, repeated mild daily stressors have been associated with exacerbation of rheumatoid arthritis (1, 2), ulcerative colitis (3), inflammatory bowel disease (4), and asthma (5). Patients with rheumatoid arthritis (6) cite stress as the most frequent antecedent of symptom flares, and stress management interventions can reduce symptoms (7). Similarly, studies in animal models of arthritis (8, 9) demonstrate that stress can exacerbate disease activity. Very little is known, however, about the biological mechanisms by which stress may exert these effects.Acute stress (10, 11), as well as acute activation of neuroendocrine circuits known to be activated by stressful stimuli (12, 13), transiently suppresses the inflammatory response. However, exacerbation of inflammatory diseases has been correlated with chronic repeated exposure to stressful stimuli rather than with exposure to a single acute stressor (2-4). We hypothesized that, compared with single acute stressors, chronic repeated stress may engage differe...

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“…Therefore, we investigated whether synovial cell proliferation is inhibited by an angiogenesis inhibitor, TNP-470 (AGM-1470), using human synovial tissues engrafted into the severe combined immunodefi-ciency disease (SCID) mouse. The SCID mouse, which has defects in both humoral and cell-mediated immunities, can serve as a recipient of grafts derived from numerous human tissues (Geiler et al, 1994;Jorgensen et al, 1996;Matsuno et al, 1998;Rendt et al, 1993;Sack et al, 1994Sack et al, , 1996.…”

mentioning

confidence: 99%

“…On the other hand, TNP-470 generally amplifies human T cell activation through induction of nuclear factor-B and nuclear factor-AT, and B cell proliferation through its action on T cells (Locigno et al, 2000). To examine whether synovial cell proliferation is induced by angiogenesis, we studied the relationship between the inhibition of synovial cell proliferation and TNP-470 in RA patients by immunohistochemistry of human synovial tissues that have been engrafted into the SCID mouse (SCIDHuAg mouse) (Matsuno et al, 1998).…”

mentioning

confidence: 99%

Study of the Mechanism Involved in Angiogenesis and Synovial Cell Proliferation in Human Synovial Tissues of Patients with Rheumatoid Arthritis Using SCID Mice

Nagashima

Tanaka

Takahashi

et al. 2002

Laboratory Investigation

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SUMMARY:To examine whether synovial cell proliferation is due to angiogenesis, we studied the relationship between the inhibition of synovial cell proliferation and an angiogenesis inhibitor, TNP-470, in human synovial tissues. Human synovial tissues were implanted into the back of SCID mice (SCID-HuAg mice). Sixteen mice were divided into two groups of eight mice each: the untreated group (vehicle group) and the TNP-470-treated group that received a dose of 10 mg/kg body weight by subcutaneous injection. The number of blood vessels and synovial lining cells clearly increased in the vehicle group, but the number of synovial lining cells clearly decreased and the blood vessels were hardly detected in the TNP-470 group. Immunohistochemically, cells that stained positively for the anti-proliferating cell nuclear antigen (PCNA) mAb were abundant in synovial lining cells and endothelial cells in synovial tissues. Cells that stained positively for the anti-CD34 polyclonal antibody were abundant in the endothelial cells in the vehicle group, but these positively stained cells were hardly detected in the TNP-470 group. The PCNA positivity ratio in the vehicle group was 0.64 Ϯ 0.019, whereas that in the TNP-470 group was 0.199 Ϯ 0.007. The numbers of cells that stained positively for anti-CD34 polyclonal antibody were 242 Ϯ 13.4 in the vehicle group and 153 Ϯ 6.73 in the TNP-470 group per 10 microscopic fields. Cells that stained positively for anti-mouse CD31 mAb were mainly localized in the synovial lining, but invaded the subsynovial lining layer in human synovial tissues. On the other hand, cells that stained positively for anti-human CD31 mAb were mainly localized in the subsynovial lining layer. We found that endothelial cell proliferation is dependent on angiogenesis based on the result that angiogenesis and synovial cell proliferation were inhibited by treatment with TNP-470. (Lab Invest 2002, 82:981-988).

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Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody: Use of rheumatoid arthritis tissue implants in the SCID mouse model

Cited by 44 publications

References 38 publications

A Critical Role for Allograft Inflammatory Factor-1 in the Pathogenesis of Rheumatoid Arthritis

A Critical Role for Allograft Inflammatory Factor-1 in the Pathogenesis of Rheumatoid Arthritis

Repeated, but not acute, stress suppresses inflammatory plasma extravasation

Study of the Mechanism Involved in Angiogenesis and Synovial Cell Proliferation in Human Synovial Tissues of Patients with Rheumatoid Arthritis Using SCID Mice

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