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Granulocyte-macrophage colony-stimulating factor and IFN-gamma restore the systemic TNF-alpha response to endotoxin in lipopolysaccharide-desensitized mice.
J Immunol. 1997 Mar 15; 158(6):2862-71.JI

Abstract

The influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma on the restoration of impaired TNF-alpha release in LPS-desensitized mice or their refractory macrophages was investigated. Mice pretreated with GM-CSF or IFN-gamma (50 microg/kg i.v.) and injected with 3 mg/kg LPS i.p. displayed increased plasma TNF-alpha levels compared with LPS controls. IL-10 was marginally up-regulated by GM-CSF but abrogated by IFN-gamma pretreatment. LPS-tolerant mice (30 microg/kg LPS i.p., -24 h) showed an attenuated plasma TNF-alpha and IL-10 response to LPS and survived LPS shock. Pretreatment of such mice with GM-CSF or IFN-gamma restored the previously impaired TNF-alpha response. In cultures of murine monocyte/macrophage-containing cell populations, i.e., alveolar, peritoneal, spleen, bone marrow cells, or blood, the presence of GM-CSF or IFN-gamma (10 ng/ml) resulted in an enhanced release of TNF-alpha initiated by 1 microg/ml LPS. Cells from LPS-tolerant mice showed a diminished responsiveness to LPS. However, when exposed to GM-CSF or IFN-gamma ex vivo, their TNF-alpha response to LPS was partially restored. These findings characterize GM-CSF and IFN-gamma as potent enhancers of LPS-induced TNF-alpha production in normal as well as in experimentally immunocompromised mice and provide the rationale for further experiments to explore the pharmacologic use of these cytokines for restoration of immunocompetence in sepsis-associated immunosuppression.

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Authors+Show Affiliations

Bundschuh DS
Biochemical Pharmacology, University of Konstanz, Germany.
Barsig J
No affiliation info available
Hartung T
No affiliation info available
Randow F
No affiliation info available
Döcke WD
No affiliation info available
Volk HD
No affiliation info available
Wendel A
No affiliation info available

MeSH

Adjuvants, ImmunologicAnimalsCells, CulturedDesensitization, ImmunologicDrug SynergismFemaleGranulocyte-Macrophage Colony-Stimulating FactorImmune ToleranceInjections, IntraperitonealInjections, IntravenousInterferon-gammaInterleukin-10LipopolysaccharidesMacrophagesMaleMiceMice, Inbred BALB CMonocytesTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9058823

Citation

Bundschuh, D S., et al. "Granulocyte-macrophage Colony-stimulating Factor and IFN-gamma Restore the Systemic TNF-alpha Response to Endotoxin in Lipopolysaccharide-desensitized Mice." Journal of Immunology (Baltimore, Md. : 1950), vol. 158, no. 6, 1997, pp. 2862-71.
Bundschuh DS, Barsig J, Hartung T, et al. Granulocyte-macrophage colony-stimulating factor and IFN-gamma restore the systemic TNF-alpha response to endotoxin in lipopolysaccharide-desensitized mice. J Immunol. 1997;158(6):2862-71.
Bundschuh, D. S., Barsig, J., Hartung, T., Randow, F., Döcke, W. D., Volk, H. D., & Wendel, A. (1997). Granulocyte-macrophage colony-stimulating factor and IFN-gamma restore the systemic TNF-alpha response to endotoxin in lipopolysaccharide-desensitized mice. Journal of Immunology (Baltimore, Md. : 1950), 158(6), 2862-71.
Bundschuh DS, et al. Granulocyte-macrophage Colony-stimulating Factor and IFN-gamma Restore the Systemic TNF-alpha Response to Endotoxin in Lipopolysaccharide-desensitized Mice. J Immunol. 1997 Mar 15;158(6):2862-71. PubMed PMID: 9058823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Granulocyte-macrophage colony-stimulating factor and IFN-gamma restore the systemic TNF-alpha response to endotoxin in lipopolysaccharide-desensitized mice. AU - Bundschuh,D S, AU - Barsig,J, AU - Hartung,T, AU - Randow,F, AU - Döcke,W D, AU - Volk,H D, AU - Wendel,A, PY - 1997/3/15/pubmed PY - 1997/3/15/medline PY - 1997/3/15/entrez SP - 2862 EP - 71 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 158 IS - 6 N2 - The influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma on the restoration of impaired TNF-alpha release in LPS-desensitized mice or their refractory macrophages was investigated. Mice pretreated with GM-CSF or IFN-gamma (50 microg/kg i.v.) and injected with 3 mg/kg LPS i.p. displayed increased plasma TNF-alpha levels compared with LPS controls. IL-10 was marginally up-regulated by GM-CSF but abrogated by IFN-gamma pretreatment. LPS-tolerant mice (30 microg/kg LPS i.p., -24 h) showed an attenuated plasma TNF-alpha and IL-10 response to LPS and survived LPS shock. Pretreatment of such mice with GM-CSF or IFN-gamma restored the previously impaired TNF-alpha response. In cultures of murine monocyte/macrophage-containing cell populations, i.e., alveolar, peritoneal, spleen, bone marrow cells, or blood, the presence of GM-CSF or IFN-gamma (10 ng/ml) resulted in an enhanced release of TNF-alpha initiated by 1 microg/ml LPS. Cells from LPS-tolerant mice showed a diminished responsiveness to LPS. However, when exposed to GM-CSF or IFN-gamma ex vivo, their TNF-alpha response to LPS was partially restored. These findings characterize GM-CSF and IFN-gamma as potent enhancers of LPS-induced TNF-alpha production in normal as well as in experimentally immunocompromised mice and provide the rationale for further experiments to explore the pharmacologic use of these cytokines for restoration of immunocompetence in sepsis-associated immunosuppression. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9058823/Granulocyte_macrophage_colony_stimulating_factor_and_IFN_gamma_restore_the_systemic_TNF_alpha_response_to_endotoxin_in_lipopolysaccharide_desensitized_mice_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=9058823 DB - PRIME DP - Unbound Medicine ER -
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