Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin‐4

Abstract

Objective. To assess CD23 status in rheumatoid arthritis (RA) patients, as defined by the levels of CD23 expression on peripheral blood mononuclear cells (PBMC), the levels of soluble CD23 (sCD23) in sera, and the production of sCD23 by PBMC cultures and its regulation by interleukin‐4 (IL‐4). Methods. CD23 expression as determined by double fluorescence‐activated cell sorter analysis and sCD23 production as determined by immunoradiometric assay were investigated in 24 RA patients and 21 controls. Soluble CD23 was measured in sera and supernatants of PBMC, activated with polyclonal activators (pokeweed mitogen [PWM] or Staphylococcus aureus Cowan strain 1, [SAC]) used either alone or in combination with IL‐2 or IL‐4. Results. The percentage of B cells expressing CD23 and serum levels of sCD23 were increased in patients with RA. IL‐4 was a potent inducer of sCD23 production in supernatants, whereas IL‐2 was inactive. Costimulation with SAC or PWM did not increase the effect obtained with IL‐4 alone. When sCD23 levels in RA and control supernatants were compared, spontaneous production was found to be increased in RA PBMC. This difference from control values was even more pronounced when sCD23 levels in PBMC and purified B cells in response to IL‐4, either alone or in combination with SAC or PWM, were tested. In the same supernatants, the increased secretion of sCD23 induced by IL‐4 was associated with an inhibitory effect of IL‐4 on Ig production, a phenomenon that was more pronounced in RA PBMC than in controls. Conclusion. CD23 status in RA is characterized by increased expression of CD23 on B cells, increased production of sCD23 in sera and supernatants, and increased sensitivity of RA PBMC and B cells to IL‐4.

Triggering of CD23b antigen by anti‐CD23 monoclonal antibodies induces interleukin‐10 production by human macrophages

“…In addition, CD23 ligation did not affect the production of other cytokines such as macrophage-CSF (data not shown) indicating that CD23 stimulation cannot be considered as nonspecific. Finally, our data extend those of Donelly et al [20] and Chomarat et al [22], demonstrating that IL-10 production by human macrophages can also be obtained after ligation of the CD23 molecule and, thus, could play an important role in the regulation of CD23-dependent immune and inflammatory responses.…”

The Th1/Th2 cytokine balance in arthritis

“…Results with very sensitive IL-4 assays indicated that activated RA whole blood cells produced more IL-4 than did controls, and with a higher IL-4:IFNy ratio. Such findings are consistent with the increased produc tion in blood as well as in activated peripheral blood mononuclear cell supernatants of soluble CD23, the production of which is enhanced by IL-4 (56). results are in contrast to those found in the RA syno vium, where a Thl pattern is predominant.…”

Ligation of CD11b and CD11c β2 integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β production in primary human monocytes through a pathway dependent on nuclear factor–κB

“…52,78 On the other hand, high levels of sCD23 have been detected in serum and synovial fluids of patients with rheumatoid arthritis and associated with worsening of the disease. [79][80][81] Synovial macrophages also express high levels of CD23 and its counter-ligands CD11b and CD11c. 80,82 These data suggest that an interaction of sCD23 or CD23 expressed on macrophages with CD11b or CD11c could play a major part in production of MIP-1␣ and MIP-1␤ in the joint and may therefore constitute an important mechanism sustaining continuous recruitment of inflammatory cells and maintaining chronic inflammation.…”