title: 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.
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, FoxP3hi/CD25hi/CD127loregulatory 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.
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Rumel Ahmed
authors.affiliation: 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.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Newman
authors.affiliation: Immcell Ltd, Swords Business Park, Swords, County Dublin, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: O'Daly
authors.affiliation: Immcell Ltd, Swords Business Park, Swords, County Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Duffy
authors.affiliation: 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.
authors.forename: Gillian
authors.initials: G
authors.lastname: Grafton
authors.affiliation: 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.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brady
authors.affiliation: Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Celentyx Ltd, Birmingham Research Park, Edgbaston, Birmingham B15 2SQ, UK.
authors.forename: S
authors.initials: S
authors.lastname: John Curnow
authors.affiliation: 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.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Barnes
authors.affiliation: Celentyx Ltd, Birmingham Research Park, Edgbaston, Birmingham B15 2SQ, UK; College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: j.gordon@bham.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Gordon
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D053804:Granzymes / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016130:Immunophenotyping; D007288:Inosine / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014777:Virus Diseases / Q000188:drug therapy*; D062366:para-Aminobenzoates / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D007155:Immunologic Factors; D062366:para-Aminobenzoates; C023730:Acedoben; D054353:Perforin; D007288:Inosine; D053804:Granzymes
keywords: Immunodeficiency; Immunomodulation; NK cell; Treg