Soluble CD23 potentiates interleukin‐1‐induced secretion of interleukin‐6 and interleukin‐1 receptor antagonist by human monocytes

Abstract

The low-affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro-inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)-1-stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25-kDa sCD23 significantly enhanced the production of IL-6 in whole blood stimulated by IL-1, but had only little or no effect in the absence of IL-1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL-1 together also enhance the production of regulating factors exhibiting anti-cytokine activities. Our data indicate that sCD23 augments the release of IL-1 receptor antagonist induced by IL-1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL-1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.

Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

“…IL-6, IL-10, CXCL13, IP-10, neopterin, and TNFα also can be produced by activated macrophages (36-39). While initially considered to be a TH2 cytokine, IL-10 is produced by regulatory T cells (Treg) (40), and by monocyte/macrophages, and is a potent B cell-stimulatory factor (41).…”

Mechanisms of IgE Inflammation

“…Although the name implies low-affinity binding, it displays only 1 logarithm difference in binding compared with the high-affinity IgE receptor, with an equilibrium dissociation constant or binding affinity of 10 8 M -1 for IgE antigen and 10 7 M -1 for IgE alone (Table 3) [40]. Unlike other Fc receptors that are structurally classified in the immunoglobulin-like superfamily, CD23 is a C-type lectin, type 2 transmembrane protein with an intracytoplasmic C terminus [40]. CD23 binds to the Cε3 domain of IgE, which is close to but differs from the FcεRI binding site [7].…”

HIV-associated immune dysfunction and viral infection: role in the pathogenesis of AIDS-related lymphoma

“…In fact, this marker is directly involved in Interleukin (IL) 4-mediated IgH CSR [28, 29], which, as noted earlier, is thought to contribute to lymphomagenesis. In addition to this, sCD23 is able to up-regulate monocyte production of IL6 [30], which is also elevated preceding the diagnosis of certain subtypes of AIDS-NHL [31, 32]. IL6, besides being a marker of immune activation, also contributes to IgH CSR in activated B cells [33], thereby having the potential to also contribute to the development of these B-cell malignancies [31].…”