VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis.

Abstract

The goal of this study was to assess the capacity of VBP15, a dissociative steroidal compound, to reduce pro-inflammatory cytokine expression in vitro, to reduce symptoms of colitis in the trinitrobenzene sulfonic acid-induced murine model, and to assess the effect of VBP15 on growth stunting in juvenile mice. In vitro studies were performed in primary human intestinal epithelial cells. Colitis was induced in mice by administering trinitrobenzene sulfonic acid. Growth stunting studies were performed in wild type outbred mice. Cells were treated with VBP15 or prednisolone (10μM) for 24h. Mice were subjected to 3days of VBP15 (30mg/kg) or prednisolone (30mg/kg) in the colitis study. In the growth stunting study, mice were subjected to VBP15 (10, 30, 45mg/kg) or prednisolone (10mg/kg) for 5weeks. Cytokines were measured by PCR and via Luminex. Colitis symptoms were evaluated by assessing weight loss, intestinal blood, and stool consistency. Growth stunting was assessed using an electronic caliper. VBP15 significantly reduced the in vitro production of CCL5 (p<0.001) IL-6 (p<0.001), IL-8 (p<0.05) and reduced colitis symptoms (p<0.05). VBP15 caused less growth stunting than prednisolone (p<0.001) in juvenile mice. VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects.