Inosine Acedoben Dimepranol promotes an early and sustained increase in the natural killer cell component of circulating lymphocytes: a clinical trial supporting anti-viral indications

Research output: Contribution to journalArticle

Authors

  • S Rumel Ahmed
  • James O'Daly
  • Sean Duffy
  • Catherine A Brady

External organisations

  • Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Celentyx Ltd, Birmingham Research Park, Edgbaston, Birmingham B15 2SQ, UK.
  • Immcell Ltd, Swords Business Park, Swords, County Dublin, Ireland.
  • Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Celentyx Ltd, Birmingham Research Park, Edgbaston, Birmingham B15 2SQ, UK.

Abstract

Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets - CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3(hi)/CD25(hi)/CD127(lo) regulatory T cells (Tregs), CD3-/CD56+ NK cells, and CD3+/CD56+ NKT cells - were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures. While a transient spike and dip in Treg and T-helper fractions, respectively, was noted, the outstanding consequence of IAD administration (1g po, qds) was an early and durable rise in NK cells. For half the cohort, NK cells increased as a percentage of total peripheral blood lymphocytes within 1.5h of receiving drug. By Day 5, all but one of the volunteers displayed higher NK cell percentages, such elevation - effectively a doubling or greater - being maintained at termination of study. The IAD-induced populations were as replete in Granzyme A and Perforin as basal NK cells. The novel finding of IAD boosting phenotypically competent NK numbers in healthy individuals supports the drug's indicated benefit in conditions associated with viral infection and reinforces the potential for uplift where immune performance may be compromised.

Details

Original languageEnglish
Pages (from-to)108-114
JournalInternational Immunopharmacology
Volume42
Early online date29 Nov 2016
Publication statusPublished - Jan 2017

Keywords

  • Immunodeficiency, Immunomodulation, NK cell, Treg