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Impact of an H3/4 Receptor Antagonist on Chemokine and Cytokine Synthesis By PBMC and Dendritic Cells Derived from PBMC
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Roman Khanferyan, MD, PhD, V. Evstratova, N. Rieger, Lawrence M. DuBuske, MD, FAAAAI
Rationale: Histamine H3 and H4 histamine receptors are involved in immune modulation. Peripheral blood mononuclear cells (PBMC) and dendritic cells (DCs) derived from PBMC synthesize cytokines and chemokines which may be modulated by blockade of H3/ H4 histamine receptors.

Methods: PBMC and DCs derived from 10 healthy donors were cultivated in the presence of dual H3/4 histamine receptor antagonist Ciproxifan (10-5M). The concentrations of cytokines and chemokines in 48-hour cultures were assessed by Multiplex assays using Luminex xMAP technology.

Results: Cultivation of PBMC with the H3/4 antagonist significantly increased  secretion of IL-4, IL-13, IL-18, IL-27, IL1a and IP-10 (p<0.05) and inhibited secretion of multiple chemo- and cytokines,  SCF, GM-CSF, LIF, IL-2, -5, -6, -7, -9, -15, -31.  In DC culture Ciproxifan significantly up-regulate the secretion of SCF, GM-CSF, IL1-α and IL-5 and down-regulates the production of IL-2, IL-6, IL-15 and LIF (p<0.05). Ciproxifan increases secretion of chemokines by PBMC (Eotaxin, RANTES, MIP-1α, MIP-1β) as well as DC (MCP-1 and RANTES).

Conclusions: Histamine H3/4  receptors are involved in the regulation of secretion of cytokines and chemokines by both PBMC and DC derived from PBMC.