Anti-IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses Journal Article

   

Authors:	Betts, B. C.; St Angelo, E. T.; Kennedy, M.; Young, J. W.
Article Title:	Anti-IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses
Abstract:	Significant comorbidites and lethality complicate GVHD and its treatment. Targeting the cytokine milieu may improve GVHD control; and IL6 is an attractive candidate, given its role in dendritic cell activation and T-cell differentiation. Tocilizumab is a humanized mAb to IL6-receptor-α (IL6R-α), which is Food and Drug Administration-approved for treatment of rheumatoid arthritis. Mouse transplant models have demonstrated that IL6 blockade also improves GVHD scores and survival. Definitive immunologic effects of IL6 inhibition have not emerged given inconsistent alterations in regulatory T cells (Tregs) and suppression of T-cell proliferation. Despite on-target suppression of IL6R-α signaling in human monocyte-derived dendritic cells (moDCs) and T cells, our data show no effect on moDC maturation/activation alloreactive T-cell proliferation, Treg expansion, or allogeneic Th1/Th17 responses in vitro. These findings merit attention in any clinical trials of tocilizumab for GVHD prevention or treatment and provide a rationale for evaluating more specific inhibitors of downstream JAK2/STAT3 signaling as well. © 2011 by The American Society of Hematology.
Keywords:	signal transduction; controlled study; human cell; janus kinase 2; lymphocyte proliferation; t lymphocyte; t-lymphocytes; animals; mice; stat3 protein; cell maturation; dendritic cell; cell differentiation; regulatory t lymphocyte; dendritic cells; t-lymphocytes, regulatory; prophylaxis; graft versus host reaction; interleukin 6; stat3 transcription factor; rheumatoid arthritis; th17 cell; th1 cell; monocyte; graft vs host disease; isoantigens; cell expansion; drug indication; alloimmunity; th17 cells; interleukin 6 receptor alpha; tocilizumab; antibodies, monoclonal, humanized; receptors, interleukin-6
Journal Title:	Blood
Volume:	118
Issue:	19
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2011-11-10
Start Page:	5340
End Page:	5343
Language:	English
DOI:	10.1182/blood-2011-06-363390
PROVIDER:	scopus
PMCID:	PMC3217414
PUBMED:	21940820
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-81055133544&partnerID=40&md5=13341c40c57fb9b282f4777b78829c96
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 9 December 2011" - "CODEN: BLOOA" - "Source: Scopus"

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