The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice

Sci Rep. 2018 Apr 17;8(1):6081. doi: 10.1038/s41598-018-24274-6.


Clinicians often hesitate prescribing corticosteroids to treat corticosteroid-responsive conditions in sickle cell disease (SCD) patients because their use can be associated with complications (increased hospital readmission, rebound pain, strokes, avascular necrosis, acute chest syndrome). Consequently, SCD patients may receive suboptimal treatment for corticosteroid-responsive conditions. We conducted a preclinical trial of dissociative (vamorolone) and conventional (prednisolone) corticosteroid compounds to evaluate their effects on nociception phenotype, inflammation, and organ dysfunction in SCD mice. Prednisolone and vamorolone had no significant effects on nociception phenotype or anemia in homozygous mice. Conversely, prednisolone and vamorolone significantly decreased white blood cell counts and hepatic inflammation. Interestingly, the effects of vamorolone were milder than those of prednisolone, as vamorolone yielded less attenuation of hepatic inflammation compared to prednisolone. Compared to controls and heterozygotes, homozygotes had significant liver necrosis, which was significantly exacerbated by prednisolone and vamorolone despite decreased hepatic inflammation. These hepatic histopathologic changes were associated with increases in transaminases and alkaline phosphatase. Together, these results suggest that, even in the setting of decreasing hepatic inflammation, prednisolone and vamorolone were associated with significant hepatic toxicity in SCD mice. These findings raise the possibility that hepatic function deterioration could occur with the use of corticosteroids (conventional and dissociative) in SCD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Anemia, Sickle Cell / complications*
  • Animals
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / therapeutic use
  • Chemical and Drug Induced Liver Injury / pathology*
  • Female
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / therapeutic use
  • Inflammation / complications
  • Inflammation / drug therapy
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mice
  • Nociception / drug effects*
  • Prednisolone / adverse effects*
  • Prednisolone / therapeutic use
  • Pregnadienediols / adverse effects*
  • Pregnadienediols / therapeutic use


  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Pregnadienediols
  • VBP15 compound
  • Prednisolone