Repository corticotropin injection (H.P. Acthar® Gel) exerts direct effects on human B cells to suppress IL4/CD40L-stimulated proliferation and immunoglobulin G production in vitro (IRC11P.437)

Abstract

Effects of melanocortin peptides on human B cells were described more than two decades ago, but therapeutic applications have not been fully explored. This study examined B cell responses to a clinically available melanocortin peptide preparation, repository corticotropin gel. Peripheral blood B cells isolated from healthy donors using CD19 magnetic beads were cultured with and without Interleukin 4 (IL-4) and CD40 ligand (CD40L). Repository corticotropin or Placebo Gels were added in serial dilutions. Cultures were harvested after 7 days for measurement of secreted IgG by ELISA, B cell proliferation using CFSE and viability with trypan blue. Mean IgG in IL-4/CD40L-stimulated cultures was 241.4 ng/ml and was reduced in a dose-dependent fashion with corticotropin gel; maximal suppression was to 65.55 ng/ml (p= 0.008; n=8). Addition of Placebo Gel or dexamethasone (1μM) to IL-4/CD40L cultures resulted in no change in IgG (240.3 and 248.1 ng/ml). The effect on IgG was paralleled by inhibition of B cell proliferation. In IL4/CD40L-stimulated cultures, 61% of cells were dividing, vs 8% with corticotropin gel (p<0.0001) and 58% with Placebo Gel (ns). Inhibition of proliferation was not accompanied by increased cell death. Repository corticotropin gel exerted dose-dependent inhibition of IgG production and B cell proliferation without effects on cell viability. These data support potential efficacy of repository corticotropin gel in diseases characterized by B cell activation.