Oral ACTH (H.P. Acthar((R))Gel) inhibits IL-1 and IL-17 secretion in humans.

摘要

OBJECTIVE: We have shown that oral corticotropin hormone (ACTH) decreased clinical score, inflammatory foci and T(eff) IL-17 in fed and adoptive transferred recipient mice with experimental autoimmune encephalomyelitis (EAE). Therefore, we determined whether oral administration of ACTH had immunological and endocrinological effects and was safe in humans. METHODS: Three groups of three healthy adult volunteers were assayed for total serum ACTH, cortisol and a set of pro-inflammatory and counter-regulatory cytokines after ingested dose(s) of ACTH 4 IU (n=3), 41 IU (n=3), or 123 IU (n=3) over 5 days. RESULTS: There were no safety issues during the trial. There was no increase in total ACTH levels after day 1 or day 5. There was no significant increase in total cortisol among the groups comparing day 1 to day 5. There were significant decreases in the inflammatory cytokine IL-1 and IL-17 secretion at day 6 compared to baseline with the 123 IU dose but not after the 4 IU and 41 IU doses. CONCLUSIONS: These data provide evidence for the safety and an immunological effect of oral ACTH in humans. It is unknown if the change in IL-1 and IL-17 reflects a local GI-mediated effect or effects following systemic absorption of ACTH.