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

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Abstract

Objective and design

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.

Materials

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.

Treatment

Cells were treated with VBP15 or prednisolone (10 μM) for 24 h. Mice were subjected to 3 days of VBP15 (30 mg/kg) or prednisolone (30 mg/kg) in the colitis study. In the growth stunting study, mice were subjected to VBP15 (10, 30, 45 mg/kg) or prednisolone (10 mg/kg) for 5 weeks.

Methods

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.

Results

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.

Conclusion

VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects.

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Author notes

    Authors and Affiliations

    1. ReveraGen BioPharma Inc., 155 Gibbs St. Suite 433, Rockville, MD, 20850, USA

      Jesse M. Damsker & John M. McCall

    2. The Joseph E. Robert Center for Surgical Care, Children’s National Health System, Washington, DC, 20010, USA

      Laurie S. Conklin, Soheil Sadri & Anthony D. Sandler

    3. The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington, DC, 20010, USA

      Laurie S. Conklin, Soheil Sadri & Anthony D. Sandler

    4. Research Center for Genetic Medicine, Children’s National Health System, Washington, DC, 20010, USA

      Blythe C. Dillingham, Karuna Panchapakesan & Christopher R. Heier

    5. PharMac LLC, Boca Grande, FL, 33921, USA

      John M. McCall

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    1. Jesse M. Damsker
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    Correspondence to Jesse M. Damsker.

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    Conflict of interest

    Dr. Jesse Damsker and Dr. John McCall are employed by ReveraGen BioPharma Inc. and have stock options and founder shares, respectively.

    Financial support

    Supported by ReveraGen BioPharma Inc. Sheikh Zayed Institute for Pediatric Surgical Innovation, NIH Grant (1R41DK102235-01).

    Additional information

    Responsible Editor: John Di Battista.

    J. M. Damsker and L. S. Conklin contributed equally to this manuscript.

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    Damsker, J.M., Conklin, L.S., Sadri, S. et al. VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis. Inflamm. Res. 65, 737–743 (2016). https://doi.org/10.1007/s00011-016-0956-8

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    • DOI: https://doi.org/10.1007/s00011-016-0956-8

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