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• W2773120633 abstract "Background: TCZ has anti-B cell and anti-inflammatory properties. TCZ treatment was shown to reduce cells of myeloid lineage including monocytes (MO). We have shown that NK cells (NK) activated via ADCC in vitro produce IFNγ and is associated with antibody-mediated rejection (ABMR). Follow-up studies also showed elevated IFNγ, TNFα and IL-6 in MO and CD8+ T cells (T8) in the in vitro ADCC. This was not seen in the mixed-lymphocyte reaction (MLR). Here we examine the effect of TCZ on cytokine production in an in vitro ADCC using multi-cytokine-flow cytometry (CFC). Methods Whole blood from normal individuals was incubated overnight with irradiated allo-PBMCs pre-treated with anti-HLA Ab+ (in vitro ADCC) or - sera (MLR), w/ or w/o TCZ. IFNγ+, TNFα+ or IL-6+ cell% in NK, MO and T8 were then enumerated by CFC. Brefeldin A, a golgi complex inhibitor, in the CFC was added at 2-6 hours after initiation of ADCC for IL-6 release. Results: IFNγ+ and TNFα+ cell% in NK, MO and T8 increased in all 4 sets of ADCC tested, while those in MLR were similar to Control (Table 1). A similar trend was observed for IL-6+ cell% in 3 of 4 sets of ADCC (0.02±0.02% vs. 0±0 in Control, 1.3±0.7% vs. 0.4±0.1 and 0.3±0.4% vs. 0.01±0.02, respectively). However, the cell% was low. Addition of TCZ reduced TNFα+ cell% in MO (32% reduction) and NK (10%) in all 4 sets of ADCC, while reduction of TNFα+ cell% in T8, IFNγ+ and IL-6+ cell% in all cell populations was minimal.Table 1: Cytokine+ cell% in each cell population.**, * in ADCC: increase vs. control in 4/4 and 3/4 experiments, respectively. **, * in ADCC+TCZ: decrease vs. ADCC in 4/4 and 3/4 experiments, respectively. Conclusions: Although preliminary, these findings suggest that anti-HLA Ab-induced ADCC is a potent activator of cytokine release in NK, MO & T8. These observations suggest a potential role for ADCC in mediation of ABMR. TCZ suppressed TNFα production primarily in MO and NK, to a lesser degree, suggesting that the IL-6/IL-6R pathway is important for MO activation in ADCC. DISCLOSURE:Jordan, S.: Grant/Research Support, Genentech Roche grant support." @default.
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• W2773120633 date "2014-07-01" @default.
• W2773120633 modified "2023-10-18" @default.
• W2773120633 title "Tocilizumab (TCZ, Anti-IL-6R) Suppressed TNFα Production By Human Monocytes in an In Vitro Model of Anti-HLA Antibody (Ab)-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC)." @default.
• W2773120633 doi "https://doi.org/10.1097/00007890-201407151-00400" @default.
• W2773120633 hasPublicationYear "2014" @default.
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