Treatment of rheumatoid arthritis with anti CD4 monoclonal antibody. Open study of 25 patients with the B-F5 clone

Wendling, Daniel; Racadot, E; Morel-Fourrier, Brigitte; Wijdenes, John

doi:10.1007/bf02283116

Cited by 41 publications

(22 citation statements)

References 16 publications

(9 reference statements)

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“…Recently, it was reported that in vivo blockade of either TNF-␣ or IL-6 signals by the administration of anti-TNF-␣ monoclonal antibody, anti-IL-6 monoclonal antibody, or anti-IL-6R antibody to RA patients was clinically very effective (53)(54)(55). The clinical efficacy of these blocking antibodies strongly indicates that correction of the dysregulation in cytokine production may be a rational approach for the treatment of RA, although the pathogenesis of RA still remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase

Miyazawa¹,

Mori²,

Miyata³

et al. 1998

Journal of Biological Chemistry

209

148

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Involvement of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-6 gene expression of human fibroblast-like synoviocytes (FLSs) was assessed. p38 MAP kinase was constitutively expressed in human FLSs and activated in response to IL-1␤. A pyridinylimidazole compound, SB203580, inhibited p38 MAP kinase activity in vivo, since the activity of MAPKAP kinase-2 (a substrate of p38 MAP kinase) in IL-1␤-stimulated FLSs was totally suppressed by it. SB203580 concentrationdependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of SB203580 was dependent on de novo protein synthesis. SB203580 significantly reduced the stability of IL-6 mRNA without affecting the rate of IL-6 gene transcription. Here, we provide evidence that p38 MAP kinase is activated in response to IL-1␤ in human FLSs and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.

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Section: Discussionmentioning

confidence: 99%

Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase

Miyazawa¹,

Mori²,

Miyata³

et al. 1998

Journal of Biological Chemistry

209

148

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“…CD4 MAb have been used for the treatment of advanced RA in a limited number of patients. All of the published uncontrolled phase I and phase I1 studies using multiple dosage regimens of CD4 MAb in RA have shown a direct amelioration of arthritis activity lasting for several months (5)(6)(7)(8)(9)(10)(11)(12). Three of these studies involved the cM-T412 CD4 MAb (10)(11)(12).…”

Section: Van Der Lubbe Et Almentioning

confidence: 99%

“…the treatment of autoimmune diseases in experimental animal models (3,4), open-label studies were performed in patients with RA (5)(6)(7)(8)(9)(10)(11)(12). CD4 MAb treatment was well tolerated and induced a rapid amelioration of arthritis activity in the majority of the patients studied.…”

mentioning

confidence: 99%

A randomized, double‐blind, placebo‐controlled study of cd4 monoclonal antibody therapy in early rheumatoid arthritis

Lubbe¹,

Dijkmans²,

Markusse³

et al. 1995

Arthritis & Rheumatism

144

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Objective. To assess the efficacy of the CD4 monoclonal antibody (MAb) cM-T412 in the treatment of early rheumatoid arthritis (RA).Methods. Sixty patients were enrolled in a 6-week randomized, double-blind, placebo-controlled study investigating multiple dose regimens of cM-T412. Thirty patients subsequently were enrolled in a 9-month randomized, double-blind, placebo-controlled study investigating monthly single-dose adminiitrations of cM-T412.Results. Analysis of clinical parameters revealed no changes in arthritis activity in the groups that received CD4 MAb or the placebo group, and no difference between the groups, in either in the first or the second part of the study. The number of circulating CD4+ cells decreased substantially in the patients treated with CD4 MAb. Conclusion. CD4 MAb treatment of patients with early RA induced no therapeutic effect.Present understanding of the pathogenesis of rheumatoid arthritis (RA) is incomplete. However, accumulating evidence has indicated that the T lymphocyte orchestrates an autoimmune process (I). Therefore, surface antigens of T cells were suggested as possible targets for a specific immunotherapy .Monoclonal antibodies (MAb) against the CD4 molecule were shown to modulate the function of CD4+ T cells (2). Following the successful use of CD4 MAb in

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“…In addition, recent progress in the field of cytokine research has led to the idea that these proinflammatory cytokines might be optimal therapeutic targets for RA. In fact, recent clinical trials of anticytokine therapy for RA (5)(6)(7)(8)(9) encouraged this idea. However, the roles of the individual cytokines for the pathology of RA have not been fully dissected and understood.…”

mentioning

confidence: 99%

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Ohshima

Saeki²,

Mima³

et al. 1998

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

367

240

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To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 ؊͞؊) mice were backcrossed for eight generations into C57BL͞6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 ؊͞؊) mice and wild-type (IL-6 ؉͞؉) littermates after the induction of AIA. Although all IL-6 ؉͞؉ mice developed severe arthritis, only mild arthritis was observed in IL-6 ؊͞؊ mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 ؊͞؊ mice, whereas it was destroyed completely in IL-6 ؉͞؉ mice. In addition, comparable mRNA expression for both IL-1␤ and tumor necrosis factor ␣, but not for IL-6, was detected in the inf lamed joints of IL-6 ؊͞؊ mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1␤ or tumor necrosis factor ␣. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 ؊͞؊ mice, but they were reduced to less than half of that found in IL-6 ؉͞؉ mice. Lymph node cells of IL-6 ؊͞؊ mice produced many more Th2 cytokines than did IL-6 ؉͞؉ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.

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Treatment of rheumatoid arthritis with anti CD4 monoclonal antibody. Open study of 25 patients with the B-F5 clone

Cited by 41 publications

References 16 publications

Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase

Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase

A randomized, double‐blind, placebo‐controlled study of cd4 monoclonal antibody therapy in early rheumatoid arthritis

Interleukin 6 plays a key role in the development of antigen-induced arthritis

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