Release of Tumor Necrosis Factor, Interleukin-2, and Gamma-Interferon in Serum After Injection of Okt3 Monoclonal Antibody in Kidney Transplant Recipients

Abramowicz, Daniel; Schandené, Liliane; Goldman, Michel; Crusiaux, Alain; Vereerstraeten, Pierre; Pauw, Luc De; Wybran, Joseph; Kinnaert, Paul; Dupont, Étienne; Toussaint, C

doi:10.1097/00007890-198904000-00008

Cited by 329 publications

(108 citation statements)

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“…CsA and FK506 are thought not to inhibit IL-6 production in vitro (23). Anti-CD3 murine mAb (OKT3) actually raises IL-6 levels in transplant recipients (24,25). However, in our study, even in the patient treated with OKT3, we could not observe an increase of IL-6.…”

Section: Discussioncontrasting

confidence: 68%

Evaluation of Sequential Serum Interleukin-6 Levels in Liver Allograft Recipients

et al. 1994

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Control serum levels of IL-6 measured by ELISA in 30 healthy blood donors or volunteers were 18±S4 pg/ml (mean ± SD). Pretransplant serum levels of IL-6 in 169 adult candidates for liver transplantation were significantly higher than control in those with fulminant hepatitis (203±232 pg/ml), alcoholic cirrhosis (116±257 pg/ml), and hepatocellular carcinoma (82±105 pg/ml). With these data as background, plasma or serum levels of EL-6 were monitored in 24 adult patients after first OLT and correlated with the clinical courses and the histopathological diagnosis of rejection. Serum or plasma levels of IL-6 decreased after transplantation regardless of pretransplant value. Four patients with infection subsequently developed continuously high IL-6 values. In the 20 of 24 patients who did not have infection, significantly higher levels of IL-6 were consistently found 0-4 days before histopathological diagnosis of rejection (131±78 pg/ml) compared with significantly lower values in patients without rejection episodes (40±21 pg/ml). The elevations of IL-6 were spike shaped, did not correlate well with the histopathological grades of rejection, and were highly responsive to augmented immunosuppression. These 20 cases were classified as: group 1, no spikes of IL-6 after liver transplantation; group 2, single spike of IL-6 after liver transplantation; and group 3, multiple spikes of IL-6 after liver transplantation. The combined early and late graft loss of each group was 0% (group 1), 25% (group 2), and 67% (group 3). We conclude that daily monitored serum or plasma IL-6 levels can be a good premonitor of liver allograft rejection and also a useful predictor of long-term graft outcome.

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Section: Discussioncontrasting

confidence: 68%

Evaluation of Sequential Serum Interleukin-6 Levels in Liver Allograft Recipients

et al. 1994

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“…Importantly the Fc regions of the respective human IgG1 molecules were mutated to limit Fc receptor binding to APC and NK cells. Earlier preclinical and clinical studies showed that native anti-CD3 Ab induced CRS, owing to robust activation of T cells, and Fc receptorexpressing cells following anti-CD3 Ab-mediated crosslinking (Abramowicz et al 1989). Fc engineering of the anti-CD3 Ab significantly reduces these effects, although some degree of CRS is observed, especially following the first course.…”

Section: Anti-cd3 Ab Therapymentioning

confidence: 99%

Reestablishing T Cell Tolerance by Antibody-Based Therapy in Type 1 Diabetes

Morillon

Martin

Gojanovich

et al. 2015

Arch. Immunol. Ther. Exp.

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Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing b cells are selectively destroyed. b cell-specific T cells are considered to be the major mediators of pathology. Accordingly, most immunotherapies tested in the clinic to date have focused on reestablishing self-tolerance within the T cell compartment. Monoclonal antibodies (Ab) targeting a variety of lymphocyte surface proteins have demonstrated benefits in preclinical and clinical settings. Indeed, the use of Ab to target T cells directly or indirectly has proven to be an effective strategy to rapidly suppress b cell autoimmunity and establish tissue-specific, long-term tolerance in rodent T1D models. In this review, we describe a number of these Ab-based immunotherapies, discuss associated immune regulatory mechanisms, and highlight results obtained in T1D clinical trials.

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“…OKT3, also called muromonab-CD3, was the first generation of antibodies developed for the prevention of solid organ transplant rejection [70,71]. However, its application was associated with a severe cytokine release syndrome, which resulted from crosslinking and activation of T cell receptors by the binding of the murine antibody Fc portion to Fc receptors on human cells [72]. To limit the side effects caused by the mitogenic potential of mAbs, humanized CD3-specific Fc mutated mAbs were developed.…”

Section: Anti-cd3 Therapy: Teplizumab and Otelizumabmentioning

confidence: 99%

Immunotherapy in Autoimmune Type 1 Diabetes

Weigmann

Franke²,

Daniel³

2012

Rev Diabet Stud

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■ AbstractType 1 diabetes (T1D) is a chronic autoimmune disease affecting millions of people worldwide. The disease is characterized by the loss of self-tolerance to the insulin-producing β-cells in the pancreas, the destruction of β-cells, and finally the development of chronic hyperglycemia at diagnosis of T1D. Its incidence and prevalence are rising dramatically, highlighting the need for immunotherapeutic strategies able to prevent or treat the disease in a safe and specific manner. Immunotherapeutic strategies are being developed, and aim to restore immunological self-tolerance, thereby limiting unwanted immunity and β-cell destruction. Foxp3 + regulatory T (Treg) cells exert essential functions to maintain and restore immunological self-tolerance. The identification of the transcription factor Foxp3 as the specification factor for the Treg cell lineage facilitated our understanding in the biology of Treg generation and function. This review highlights the current understanding of immunotherapeutic approaches as preventative and curative measures for autoimmune T1D. It includes an overview on early immunointervention studies, which made use of general immunosuppressive agents such as cyclosporin A, followed by a discussion on newly emerging clinical trials. Besides non-antigenspecific therapies, particular attention is given to antigenspecific generation of Foxp3 + Treg cells and their potential use to limit autoimmunity such as T1D.

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Release of Tumor Necrosis Factor, Interleukin-2, and Gamma-Interferon in Serum After Injection of Okt3 Monoclonal Antibody in Kidney Transplant Recipients

Cited by 329 publications

References 0 publications

Evaluation of Sequential Serum Interleukin-6 Levels in Liver Allograft Recipients

Evaluation of Sequential Serum Interleukin-6 Levels in Liver Allograft Recipients

Reestablishing T Cell Tolerance by Antibody-Based Therapy in Type 1 Diabetes

Immunotherapy in Autoimmune Type 1 Diabetes

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