In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2022-2-3), p. e0263370-
Abstract:
The cytokine Interferon-γ (IFN-γ) exerts powerful immunoregulatory effects on the adaptive immune system and also enhances functions of the neutrophil (PMN). The clinical use of IFN-γ has been driven by the finding that its administration to patients with chronic granulomatous disease (CGD) results in decreased incidence and severity of infections. However, IFN-γ has no effect on the characteristic defect of CGD, the inability to convert oxygen to microbicidal metabolites including superoxide anion (O 2 - ) during the phagocytosis associated oxidative burst. We administered varying doses of IFN-γ to adult volunteers and studied the effects on plasma drug levels and response molecules and PMNs isolated from blood drawn at intervals over a 96- hour period. Plasma concentrations of IFN-γ, IP-10 and neopterin, and stimulated release of O 2 - from PMNs exhibited dose- and time-dependent increases after IFN-γ administration. Gene expression in PMNs was altered for 2775 genes; changes occurred rapidly after administration and returned to baseline in 24–36 hours. Several genes involved with neutrophil host defense were upregulated including those for components of the O 2 - generating NADPH oxidase; innate-immune and Fc receptors; proteins involved in MHCI and II; a regulator of circulating PMN number; guanylate binding proteins; and a key enzyme in synthesis of an essential NOS cofactor. Coordinate changes were detected in protein levels of representative products from several of these genes. Lysates from isolated neutrophils also demonstrated a spike in NO following IFN-γ administration. IFN-γ appears to increase non-oxygen dependent microbicidal functions of PMNs which could provide strategies to compensate for deficiencies, explain its clinical benefit for CGD patients and expand therapeutic applications of IFN-γ to other disorders. Trial registration: Protocol registered in ClinicalTrials.gov, NCT02609932 , Effect of IFN-γ on Innate Immune Cells.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0263370
DOI:
10.1371/journal.pone.0263370.g001
DOI:
10.1371/journal.pone.0263370.g002
DOI:
10.1371/journal.pone.0263370.g003
DOI:
10.1371/journal.pone.0263370.g004
DOI:
10.1371/journal.pone.0263370.g005
DOI:
10.1371/journal.pone.0263370.g006
DOI:
10.1371/journal.pone.0263370.g007
DOI:
10.1371/journal.pone.0263370.g008
DOI:
10.1371/journal.pone.0263370.t001
DOI:
10.1371/journal.pone.0263370.t002
DOI:
10.1371/journal.pone.0263370.t003
DOI:
10.1371/journal.pone.0263370.s001
DOI:
10.1371/journal.pone.0263370.s002
DOI:
10.1371/journal.pone.0263370.s003
DOI:
10.1371/journal.pone.0263370.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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