Tags

Type your tag names separated by a space and hit enter

In vitro prevention and reversal of lipopolysaccharide desensitization by IFN-gamma, IL-12, and granulocyte-macrophage colony-stimulating factor.
J Immunol. 1997 Mar 15; 158(6):2911-8.JI

Abstract

LPS tolerance is characterized by a diminished monocytic synthesis of TNF-alpha and, interestingly, IL-10 after LPS restimulation. We wondered whether granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-12, and IFN-gamma can prevent or reverse this down-regulation of TNF-alpha and IL-10 production. The LPS-induced TNF-alpha amounts in desensitized PBMC treated with GM-CSF, IFN-gamma, or IL-12 and in naive, non-cytokine-primed cultures were similar, while much more TNF-alpha was induced in cytokine-primed naive cells. The effect of IL-12 was dependent on the presence of nonmonocytic cells and could be completely blocked with an IFN-gamma antiserum. Treatment of LPS-desensitized pure monocytes with IFN-gamma or GM-CSF resulted in a very high TNF-alpha expression and no difference to cytokine-primed naive monocytes was evident any longer. While IFN-gamma and IL-12 decreased IL-10 expression in naive PBMC, it was increased by both and by GM-CSF in LPS-tolerant cultures. Again, only IL-12 was dependent on the presence of nonmonocytic cells. For prevention of LPS tolerance, similar results were obtained. Recently, we have shown that IL-10 and TGF-beta mediate LPS desensitization in vitro and can be used to establish LPS hyporesponsiveness in the absence of LPS. IFN-gamma and GM-CSF prevented and reversed down-regulation of TNF-alpha and IL-10 synthesis also in the model of IL-10/TGF-beta1-induced LPS hyporesponsiveness, while IL-12 was ineffective because of its obvious inability to induce IFN-gamma. In summary, after LPS desensitization/hyporesponsiveness, IFN-gamma and GM-CSF tended to normalize pro- and anti-inflammatory monocytic behavior. Our results suggest that during LPS desensitization/hyporesponsiveness, monocytes acquire a hitherto unknown functional state with an altered reaction to biologic response modifiers.

Authors+Show Affiliations

Institute of Medical Immunology, Charité Medical School, Humboldt-University Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9058829

Citation

Randow, F, et al. "In Vitro Prevention and Reversal of Lipopolysaccharide Desensitization By IFN-gamma, IL-12, and Granulocyte-macrophage Colony-stimulating Factor." Journal of Immunology (Baltimore, Md. : 1950), vol. 158, no. 6, 1997, pp. 2911-8.
Randow F, Döcke WD, Bundschuh DS, et al. In vitro prevention and reversal of lipopolysaccharide desensitization by IFN-gamma, IL-12, and granulocyte-macrophage colony-stimulating factor. J Immunol. 1997;158(6):2911-8.
Randow, F., Döcke, W. D., Bundschuh, D. S., Hartung, T., Wendel, A., & Volk, H. D. (1997). In vitro prevention and reversal of lipopolysaccharide desensitization by IFN-gamma, IL-12, and granulocyte-macrophage colony-stimulating factor. Journal of Immunology (Baltimore, Md. : 1950), 158(6), 2911-8.
Randow F, et al. In Vitro Prevention and Reversal of Lipopolysaccharide Desensitization By IFN-gamma, IL-12, and Granulocyte-macrophage Colony-stimulating Factor. J Immunol. 1997 Mar 15;158(6):2911-8. PubMed PMID: 9058829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro prevention and reversal of lipopolysaccharide desensitization by IFN-gamma, IL-12, and granulocyte-macrophage colony-stimulating factor. AU - Randow,F, AU - Döcke,W D, AU - Bundschuh,D S, AU - Hartung,T, AU - Wendel,A, AU - Volk,H D, PY - 1997/3/15/pubmed PY - 1997/3/15/medline PY - 1997/3/15/entrez SP - 2911 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 158 IS - 6 N2 - LPS tolerance is characterized by a diminished monocytic synthesis of TNF-alpha and, interestingly, IL-10 after LPS restimulation. We wondered whether granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-12, and IFN-gamma can prevent or reverse this down-regulation of TNF-alpha and IL-10 production. The LPS-induced TNF-alpha amounts in desensitized PBMC treated with GM-CSF, IFN-gamma, or IL-12 and in naive, non-cytokine-primed cultures were similar, while much more TNF-alpha was induced in cytokine-primed naive cells. The effect of IL-12 was dependent on the presence of nonmonocytic cells and could be completely blocked with an IFN-gamma antiserum. Treatment of LPS-desensitized pure monocytes with IFN-gamma or GM-CSF resulted in a very high TNF-alpha expression and no difference to cytokine-primed naive monocytes was evident any longer. While IFN-gamma and IL-12 decreased IL-10 expression in naive PBMC, it was increased by both and by GM-CSF in LPS-tolerant cultures. Again, only IL-12 was dependent on the presence of nonmonocytic cells. For prevention of LPS tolerance, similar results were obtained. Recently, we have shown that IL-10 and TGF-beta mediate LPS desensitization in vitro and can be used to establish LPS hyporesponsiveness in the absence of LPS. IFN-gamma and GM-CSF prevented and reversed down-regulation of TNF-alpha and IL-10 synthesis also in the model of IL-10/TGF-beta1-induced LPS hyporesponsiveness, while IL-12 was ineffective because of its obvious inability to induce IFN-gamma. In summary, after LPS desensitization/hyporesponsiveness, IFN-gamma and GM-CSF tended to normalize pro- and anti-inflammatory monocytic behavior. Our results suggest that during LPS desensitization/hyporesponsiveness, monocytes acquire a hitherto unknown functional state with an altered reaction to biologic response modifiers. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9058829/In_vitro_prevention_and_reversal_of_lipopolysaccharide_desensitization_by_IFN_gamma_IL_12_and_granulocyte_macrophage_colony_stimulating_factor_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=9058829 DB - PRIME DP - Unbound Medicine ER -