Interferon-gamma (IFN-γ) as a potential radio- and chemo-protectant

Abstract

Interferons (IFN) have had increasing clinical usage in the treatment of a variety of disorders, at times being used in combination with chemo-or radiotherapy. However, interferons may have inhibitory effects on hematopoietic stem cell proliferation and the effects of this cytokine's use on long-term hematologic function have not been studied. We performed the competitive repopulation assay in the murine system, using cells exposed to irradiation or single-dose chemotherapy with or without concomitant IFN-␥ use. IFN-␥ alone had no deleterious effects on hematopoietic stem cell productivity. We measured the repopulating ability of exhaustible multilineage precursors that were present at early stages of marrow repopulation after competitive repopulation (30 days). These progenitors were minimally impacted by cyclophosphamide (CTX) with or without IFN-␥. Irradiation (XRT) and CTX alone produced significant repopulating defects in the most primitive hematopoietic stem cell, PHSC. Addition of IFN to either treatment regimen resulted in protection of PHSC, with improved repopulating ability, although the levels of donor marrow reached control levels only when CTX and IFN were used together. The results of multiple use of IFN with chemotherapy must be studied further, but IFN may offer hematologic radio-and chemoprotection, in addition to its antitumor properties in clinical protocols for treatment of cancers. Am.

Physiological functions of TNF family receptor/ligand interactions in hematopoiesis and transplantation

“…29,35,38 The influence of growth factors has been long recognized, 73 with subsequent identification of the involvement of toll-like receptors 74 and cytokines such as interferons a and g, which suppress and induce hematopoietic progenitor function upon tonic and phasic exposure, respectively. 75,76 Similar differential effects are observed for short and sustained TNF receptor activation, 77,78 which induces transcription of different sets of genes controlled by NF-kB and has distinct consequences under various experimental conditions. 7-17,70,72 Identification of multiple functions of TNF superfamily receptor/ligand interactions in hematopoietic cells questions the physiological significance.…”

Pathogenicity of Bordetella avium under immunosuppression induced by Reticuloendotheliosis virus in specific-pathogen-free chickens

“…IFN-g is also involved in protecting against harmful pathogenic organisms [27]. It performs as the chemo-and radio-protectants [28], and as an immunoenhancement against tumors [29], bacteria [30], viruses [31], and parasites [32]. The sensitivity and specificity of the chicken IFN-g ELISA was of sufficient magnitude to permit its detection in serum sample and demonstrated good correlation with IFN-g bioassay.…”

Long term hematopoeitic damage after chemotherapy and cytokine

“…A number of cytokines, including IL-1, SCF, IL-6, MIP1-alpha, TNF-alpha, interferon-gamma (IFNgamma), interleukin-11 (IL-11), have been reported to protect hematopoietic progenitors against the myelotoxic effects of chemotherapy (96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110).…”

“…Exceptions to this general rule do exist, however. For instance, Gardner investigated the ability of IFN-gamma, given as a single dose, to protect PHSC using the competitive repopulating assay (106). Addition of IFNgamma to the treatment with cyclophosphamide improved repopulating ability of PHSC, with repopulating ability of treated marrow returning to levels comparable to control marrow.…”