Potentiation ofin vitrosynthesis of human IgE by cyclosporin A (CsA)

Abstract

SUMMARYIn this study, we investigated the moduiatory effects of CsA on in vitro synthesis of IgE. IgGI and lgG4 by human peripheral blood mononuclear cells (PBMC). In contrast to its known immunosuppressive elTect, we have demonstrated that a low dose of CsA (IO'^M. l20ng/ml) potentiated IgE production by up to 40-fold (i.e. from 33±4 5 to 1346±290 ng/nil). This potentiation was specific for IgE, since no such effect was demonstrable with IgGI and IgG4. Potentiation of IgE synthesis by CsA in the PBMC cultures was partly due to CsA acting on T cells, as demonstrated by the addition of CsA-treated T cells to T cell-depleted cultures. However, potentiation was also demonstrable in a T cell-depleted. anti-CD40-stimulated culture (four-fold increase from 400 ± 48 to 1606 ± 127 ng/nil). Our data therefore suggest that there are at least two mechanisms for CsAinduced potentiation of IgE synthesis, one T cell-dependent and the other T cell-independent. The clinical implications of these findings are discussed with regard to the use of CsA in the treatment of Th2-mcdiated diseases.

Efficacy and safety of long‐term treatment with cyclosporin A for atopic dermatitis

“…The literature suggests a role for CsA in this phenomenon. [11][12][13] Surprisingly, our results are, in this aspect, in contrast to previous studies, which have been reviewed by Naeyaert et al . 14 They conclude from 13 published studies that there is no evidence for a rebound phenomenon after stopping CsA.…”

“…Although observational and highly speculative, we suggest that CsA treatment may be related to this rebound phenomenon with increasing serum IgE levels that was observed in a subpopulation of AD patients. The literature suggests a role for CsA in this phenomenon 11–13 . Surprisingly, our results are, in this aspect, in contrast to previous studies, which have been reviewed by Naeyaert et al 14 .…”

A First in Human Trial to Evaluate the Safety and Immunogenicity of a G Protein Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18-45 Years

“…It can induce antigen-specific T regulatory cells (Tregs) to ultimately achieve tolerogenic responses when combined with a protein antigen at a certain ratio and under a certain dose level [22]. In the development of BARS13, CsA was successfully used to generate tolerogenic responses with human PBMC in vitro [23]. As Treg plays an essential role in the suppression of VED [24], BARS13 was developed using a combination of the RSV-G with CsA to induce functional Tregs and a high level of neutralizing anti-RSV antibodies.…”

A First-in-Human Trial to Evaluate the Safety and Immunogenicity of a G Protein-Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18–45 Years of Age

“…It can induce antigen-specific T regulatory cells (Tregs) to ultimately achieve tolerogenic responses when combined with a protein antigen at a certain ratio and under a certain dose level [ 22 ]. In the development of BARS13, CsA was successfully used to generate tolerogenic responses with human PBMCs in vitro [ 23 ]. As Treg plays an essential role in the suppression of VED [ 24 ], BARS13 was developed using a combination of RSV-G with CsA to induce functional Tregs and a high level of neutralizing anti-RSV antibodies.…”