Mifepristone (RU486) restores humoral and T cell‐mediated immune response in endotoxin immunosuppressed mice

Sepsis and septic shock can be caused by Gram‐positive and ‐negative bacteria and other microorganisms. In the case of Gram‐negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the...

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Vydáno v:	Clinical and experimental immunology Ročník 162; číslo 3; s. 568 - 577
Hlavní autoři:	Rearte, B, Maglioco, A, Balboa, L, Bruzzo, J, Landoni, V.I, Laborde, E.A, Chiarella, P, Ruggiero, R.A, Fernández, G.C, Isturiz, M.A
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Oxford, UK Blackwell Publishing Ltd 01.12.2010 Blackwell Oxford University Press Blackwell Science Inc
Témata:	Analytical, structural and metabolic biochemistry Animal Models Animals Antigens, CD - biosynthesis Biological and medical sciences Cyclophosphamide - administration & dosage Cytokines Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives endotoxin tolerance Forkhead Transcription Factors - biosynthesis Fundamental and applied biological sciences. Psychology glucocorticoids Immune system Immunity, Cellular - drug effects Immunity, Humoral - drug effects Immunosuppression Immunosuppressive Agents - administration & dosage Lipopolysaccharides - administration & dosage Medical research Mice Mice, Inbred BALB C Mifepristone - administration & dosage Mifepristone - pharmacology Receptors, Glucocorticoid - antagonists & inhibitors Rodents RU486 T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - metabolism T-Lymphocytes - pathology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - pathology Antineoplastic agent Immune response RU486 Rodentia Tolerance Biochemistry Cellular immunity Antihormone Endotoxin Glucocorticoid Toxin Vertebrata Immunosuppression Mammalia Mouse Animal Antiprogesterone Mifepristone glucocorticoids endotoxin tolerance Humoral immunity
ISSN:	0009-9104, 1365-2249, 1365-2249
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Shrnutí:	Sepsis and septic shock can be caused by Gram‐positive and ‐negative bacteria and other microorganisms. In the case of Gram‐negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)‐α, interleukin (IL)‐1, IL‐6, interferon (IFN)‐γ and the concomitant induction of anti‐inflammatory mediators such as IL‐10, transforming growth factor (TGF)‐β or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non‐specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4⁺CD25⁺forkhead boxP3⁺ and GR‐1⁺CD11b⁺ cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state.
Bibliografie:	http://dx.doi.org/10.1111/j.1365-2249.2010.04262.x ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0009-9104 1365-2249 1365-2249
DOI:	10.1111/j.1365-2249.2010.04262.x