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
| Autor: | S. John Curnow, Sean Duffy, Amy S Newman, S. Rumel Ahmed, John Gordon, Catherine A. Brady, Nicholas M. Barnes, Gillian Grafton, James O'Daly |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
T-Lymphocytes Immunology chemical and pharmacologic phenomena Lymphocyte Activation CD19 Granzymes Natural killer cell Immunophenotyping Cohort Studies 03 medical and health sciences Interleukin 21 0302 clinical medicine Immune system Antigens CD Antineoplastic Combined Chemotherapy Protocols medicine para-Aminobenzoates Immunology and Allergy Humans Immunologic Factors Cells Cultured Pharmacology B-Lymphocytes biology Perforin Natural killer T cell Healthy Volunteers Inosine Lymphocyte Subsets Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Virus Diseases biology.protein Interleukin 12 Antibody 030215 immunology |
| Zdroj: | International immunopharmacology. 42 |
| ISSN: | 1878-1705 |
| Popis: | 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/CD127lo 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. |
| Databáze: | OpenAIRE |
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