Up-regulation by cyclosporine (CsA) of the in vitro release of soluble CD23 (sCD23) and of the in vitro production of IL-6 and IgM.
In the present study, we examined the effect of CsA on the in vitro production of Ig and on the in vitro production of molecules known to have B-cell growth and differentiation activities, such as IL-6 and sCD23. For the purpose of this study, we developed an experimental in vitro system closely resembling an in vivo model of ongoing B-cell activation. Pre-activated B cells proliferated and produced IgM optimally when they were re-cultured in the presence of IL-2/IL-6. CsA down-regulated the IL-2/IL-6-induced proliferative responses of pre-activated B cells by at least 50%, but it up-regulated IgM production in the same experiments. This up-regulating effect was not cytokine-related since it was also seen when cells were re-cultured in the absence of any cytokines. Optimal release of sCD23 was observed when SAC-pre-activated B cells were re-cultured in the presence of IL-4 or IL-4 plus IL-2 and CsA up-regulated significantly the release of this molecule in these cultures. Finally, CsA was shown to inhibit PHA-induced cell proliferation of PBMC and to up-regulate IL-6 production in the same cultures. We conclude that CsA can amplify in vitro both the production of Ig and the release of sCD23 by pre-activated B cells. This finding, in combination with the CsA-induced up-regulation of lectin-induced IL-6 production, may have clinical implications in disease states with an ongoing immune activation, where prolonged administration of CsA might be anticipated.
Hornung
N
N
Department of Surgery, Nykøbing Mors Hospital, Denmark.
Degiannis
D
D
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D017455:Receptors, IgE / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D007075:Immunoglobulin M; D015850:Interleukin-6; D017455:Receptors, IgE; D016572:Cyclosporine