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


METHODS
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.


METHODS
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.


CONCLUSIONS
VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects.
ReveraGen BioPharma Inc., 155 Gibbs St. Suite 433, Rockville, MD, 20850, USA. Jesse.Damsker@reveragen.com.
Jesse M
JM
Damsker
The Joseph E. Robert Center for Surgical Care, Children's National Health System, Washington, DC, 20010, USA.|The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, DC, 20010, USA.
Laurie S
LS
Conklin
The Joseph E. Robert Center for Surgical Care, Children's National Health System, Washington, DC, 20010, USA.|The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, DC, 20010, USA.
Soheil
S
Sadri
Research Center for Genetic Medicine, Children's National Health System, Washington, DC, 20010, USA.
Blythe C
BC
Dillingham
Research Center for Genetic Medicine, Children's National Health System, Washington, DC, 20010, USA.
Karuna
K
Panchapakesan
Research Center for Genetic Medicine, Children's National Health System, Washington, DC, 20010, USA.
Christopher R
CR
Heier
ReveraGen BioPharma Inc., 155 Gibbs St. Suite 433, Rockville, MD, 20850, USA.|PharMac LLC, Boca Grande, FL, 33921, USA.
John M
JM
McCall
The Joseph E. Robert Center for Surgical Care, Children's National Health System, Washington, DC, 20010, USA.|The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, DC, 20010, USA.
Anthony D
AD
Sandler
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049628:Body Size / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011244:Pregnadienediols / Q000494:pharmacology / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D011244:Pregnadienediols; C584811:VBP15 compound; D014302:Trinitrobenzenesulfonic Acid
Autoimmunity; Glucocorticoids; Inflammation; Inflammatory bowel disease