Differential effects of the tumor necrosis factor alpha-blocker infliximab and etanercept on immunocompetent cells in vitro

Thaher, Firas; Plankenhorn, Sandra; Klein, Reinhild

doi:10.1016/j.intimp.2011.06.005

Cited by 14 publications

(20 citation statements)

References 59 publications

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“…4E). Addition of infliximab to cell cultures did not increase the level of soluble IL-2R (of which CD25 is a subunit) levels during the 7 days of cell culture (day 1; 34 (18-53) versus 22 (19)(20)(21)(22)(23)(24)(25)(26)(27)(28) + T were detectable at day one (Fig. 4 H).…”

Section: Infliximab Reduces Proliferation and Expression Of Cd25 In Tmentioning

confidence: 96%

Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis

et al. 2013

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Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti-TNF therapy-na€ ıve ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4 + and CD8 + T cell populations and inhibited secretion of IFN-c, IL-13, IL-17A, TNF as well as granzyme A. Infliximab also suppressed CD4 + and CD8 + T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen-specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3 + CD4 + T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab-mediated disease remission in patients with UC.

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Section: Infliximab Reduces Proliferation and Expression Of Cd25 In Tmentioning

confidence: 96%

Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis

et al. 2013

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“…22,34 Then, PBMC were cocultured with PPD, TT, and BCG at concentrations of 2.0 TU (tuberculin units)/mL, 1.6 IU/mL, and 5 × 10 5 bacteria/mL, respectively, as shown in recent studies to provide best results. 26,27 Proliferation assay…”

Section: Pbmc Culturesmentioning

confidence: 99%

“…[25][26][27] Ninety-six-well microtiter plates were coated with a monoclonal antibody to human cytokines (1.75 µg/mL for IL-1, IL-5, IL-6, IL-10, IL-13, TNF-α, IFN-γ, TNF-β, granulocyte/macrophage colony-stimulating factor; Pharmingen, San Diego, CA) in hydrogen bicarbonate buffer, pH 9.6, overnight at 4°C. In order to avoid nonspecific binding, wells were then blocked with 0.5% bovine serum albumin (BSA) in phosphatebuffered saline (PBS 60 mmol/L, pH 7.4) for 1 hour at room temperature.…”

Section: Cytokine Productionmentioning

confidence: 99%

“…27 Antibody cocktails were used for the demonstration of activated PBMC subpopulations (activated CD4+ T cells: FastImmune …”

Section: Flow Cytometrymentioning

confidence: 99%

“…In the first step we investigated their influence on unstimulated cells, and in the second step we mimicked inflammatory stages by preincubating the PBMC with TH1-(purified protein derivative, [PPD]), and TH2-cell activating antigens (tetanus toxoid [TT]) as well as BCG (bacillus Calmette-Guérin), stimulating mainly macrophages/monocytes. [25][26][27] It will be shown that these two fullerenes do not influence T cell reactivity but there is some evidence that they may activate cells of the innate immune system such as macrophages, dendritic cells (DC), or natural killer (NK) cells.…”

Section: Introductionmentioning

confidence: 99%

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Effect of buckminsterfullerenes on cells of the innate and adaptive immune system: an in vitro study with human peripheral blood mononuclear cells

Bunz¹,

Plankenhorn²,

Klein³

2012

IJN

Self Cite

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C60 nanoparticles, the so-called buckminsterfullerenes, have attracted great attention for medical applications as carriers, enzyme inhibitors or radical scavengers. However, publications evaluating their immunological mechanisms are still rather limited.Therefore, we aimed to analyze systematically the in vitro influence of polyhydroxy-C60 (poly-C60) and N-ethyl-polyamino-C60 (nepo-C60) on peripheral blood mononuclear cells (PBMC) from healthy individuals, angling their effect on proliferation, expression of surface markers, and cytokine production. We isolated PBMC from 20 healthy subjects and incubated them in a first step only with poly-C60 or nepo-C60, and in a second step together with recall antigens (purified protein derivative, tetanus toxoid, bacillus Calmette-Guérin). Proliferation was determined by 3 H-thymidine incorporation, activation of PBMC-subpopulations by flow cytometry by measurement of the activation marker CD69, and secretion of T helper cell type 1 (TH1)-(interferon-gamma [IFN-γ], tumor necrosis factor beta [TNF-β]), TH2-(interleukin-5 [IL-5], -13, -10) and macrophage/monocyte-related cytokines (IL-1, IL-6, TNF-α) into the supernatants by enzyme-linked immunosorbent assay. Both fullerenes did not influence T cell reactivity, with no enhanced expression of CD69 and production of T cell cytokines observed, the CD4/CD8 ratio remaining unaffected. In contrast, they significantly enhanced the release of IL-6 and CD69-expression by CD56 positive natural killer cells. PBMC, which had been cultured together with the three recall antigens were not affected by both fullerenes at all. These data indicate that fullerenes do not interact with T cell reactivity but may activate cells of the innate immune system. Furthermore, they seem to act only on 'naïve' cells, which have not been prestimulated with recall antigens, there are however, large inter individual differences.

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Impact of anti-TNF therapy on NK cells function and on immunosurveillance against B-cell lymphomas

Nocturne

Boudaoud

et al. 2017

Journal of Autoimmunity

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Differential effects of the tumor necrosis factor alpha-blocker infliximab and etanercept on immunocompetent cells in vitro

Cited by 14 publications

References 59 publications

Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis

Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis

Effect of buckminsterfullerenes on cells of the innate and adaptive immune system: an in vitro study with human peripheral blood mononuclear cells

Impact of anti-TNF therapy on NK cells function and on immunosurveillance against B-cell lymphomas

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