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Effect of IFN-γ on Innate Immune Cells

Disease Information

Descriptive Information
Brief Title † Effect of IFN-γ on Innate Immune Cells
Official Title † Effect of Interferon-gamma 1-b on Innate Immune Cells
Brief Summary The investigators hypothesize that neutrophils and monocytes developed under the influence of Interferon- gamma-1b (IFN-γ-1b, Actimmune*) in vivo will display enhanced function across a broad range of activities related in large part to the transcriptional activation effects of this cytokine. The investigators will evaluate the effects of IFN-γ in healthy human subjects in vivo on gene expression, biologic activity markers, and functional activity of myeloid cells in single dose studies and in steady state studies.
Detailed Description Named for their potent ability to interfere and protect against viral infections, interferons (IFNs) have many regulatory effects on the immune system.1 Of the members of the two classes of these compounds, IFN-γ has the most diverse and powerful immune effects. Studies have mostly evaluated IFN-γ interactions with cells of adaptive immunity, including macrophages and lymphocytes. Effects on innate immunity, particularly polymorphonuclear leukocytes or neutrophils and monocytes are less well studied. However, investigations have suggested that IFN-γ may be involved in signal transduction, gene expression, the respiratory burst and neutrophil NADPH oxidase (Nox2) activity, phagocytosis, motility, microbicidal activity, and apoptosis. Not all of these functions are enhanced by IFN-γ; but the clinical use of this cytokine has been driven, in part by these results. For example, the primary motivation for initiating investigation of its beneficial clinical effects in Chronic Granulomatous Disease (CGD) was its effects on Nox2 activity.2 Most data in this area was based on studies using differentiated neutrophils from peripheral blood.1 However, the phenotype of neutrophils developed under the influence of this cytokine, not just changes expressed by exposure of differentiated cells to IFN-γ, is critical to understanding the physiologic effects of IFN-γ and the broad applications for its use in treatment of a range of human diseases. To expand their understanding of the role of IFN-γ in the development and functional integrity of the neutrophil, the investigators have completed a series of studies with PLB-985 cells in an in vitro culture system of myeloid cells. In this proposal, the investigators will evaluate innate immune activation and phagocyte function in healthy adult volunteers who are receiving IFN-γ.
Study Phase Phase 1
Study Type † Interventional
Study Design † Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary Outcome Measure † Change in Neutrophil Nox2 activity.
Secondary Outcome Measure † Change in Neutrophil Function studies.
Condition † Chronic Granulomatous Disease
Intervention † DrugAdministration of drug (Interferon-gamma 1-b) subcutaneously
Study Arms / Comparison Groups SD or SS In this study, IFN- γ-1b will be subcutaneously administered a total of 30 subjects in one of two cohorts; Single Dose (SD) or Steady State (SS) dosing. Dosing of IFN- γ-1b will be based upon the time subject became eligible and started study. In this non-randomized, open-label study, subjects will be enrolled on the SD cohort first, and once that cohort has been filled, enrollment to the SS cohort will begin. Although not required, subjects in the SD cohort may also volunteer to participate in the SS cohort if they still meet eligibility criteria. Separate consents will be used for the SD and SS cohorts. In the event not all the SD subjects choose to continue onto the SS cohort, we will plan to recruit new participants from our local campus community.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 30
Start Date † July 2016
Completion Date November 2017
Primary Completion Date November 2017
Eligibility Criteria † Inclusion Criteria: 1. Healthy adults over the age of 18 years up to 60 years. 2. At time of screening subject is well and healthy; 3. Acute infections resolved; 4. Subject off treatment medications; 5. No diagnosis of chronic conditions or active health care issues for which the subject is actively followed by a health care provider or is on chronic medications. 6. Non-prescription medications for mild inter-current illnesses will be allowed at the discretion of the principal investigator. Exclusion Criteria: 1. Pregnancy. 2. History of current infection; 3. Two weeks from most recent intercurrent infection; 4. History of recurrent infections or immunodeficiency.
Gender Both
Ages 18 Years - 60 Years
Accepts Healthy Volunteers Accepts Healthy Volunteers
Contacts †† Amanda Kenny, MA, 303-724-2677, amanda.kenny@ucdenver.edu
Location Countries † United States
Administrative Information
NCT ID † NCT02609932
Organization ID 15-1643
Secondary IDs †† UL1TR001082
Responsible Party Sponsor
Study Sponsor † University of Colorado, Denver
Collaborators ††
Investigators † Principal Investigator: Daniel R. Ambruso, MD, University of Colorado, Denver
Information Provided By
Verification Date November 2016
First Received Date † November 11, 2015
Last Updated Date November 22, 2016
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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