Sökning: (WFRF:(Syk Ingvar)) spr:eng pers:(Lepsenyi Mattias) >
Simvastatin protect...
Simvastatin protects against T cell immune dysfunction in abdominal sepsis.
-
- Zhang, Su (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
Luo, Lingtao (författare)
-
- Wang, Yongzhi (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
visa fler...
-
- Rahman, Milladur (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
- Lepsenyi, Mattias (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
- Syk, Ingvar (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
- Jeppsson, Bengt (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
-
visa färre...
-
(creator_code:org_t)
- 2012
- 2012
- Engelska.
-
Ingår i: Shock. - 1540-0514. ; 38:5, s. 524-531
- Relaterad länk:
-
http://www.ncbi.nlm....
-
visa fler...
-
http://dx.doi.org/10...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- ABSTRACT: Sepsis-triggered immune paralysis including T-cell dysfunction increases susceptibility to infections. Statins exert beneficial effects in patients with sepsis, although the mechanisms remain elusive. Herein, we hypothesized that simvastatin may attenuate T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were pretreated with simvastatin (10 mg/kg) before cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation, and regulatory T cells (CD4CD25Foxp3) were quantified by use of flow cytometry. Formation of interferon γ (IFN-γ) and interleukin 4 (IL-4) in the spleen and plasma levels of high-mobility box group 1 (HMBG1) and IL-6 were determined using enzyme-linked immunosorbent assay. Cecal ligation and puncture caused a clear-cut increase in apoptosis and decrease in proliferation in splenic CD4 T cells. It was found that simvastatin markedly reduced apoptosis and improved proliferation in CD4 T cells in septic mice. Moreover, CLP-induced formation of regulatory T cells in the spleen was abolished in simvastatin-treated animals. Cecal ligation and puncture greatly decreased the levels of IFN-γ and IL-4 in the spleen. Simvastatin completely reversed this sepsis-mediated inhibition of IFN-γ and IL-4 formation in the spleen. We observed that CLP increased plasma levels of HMBG1 by 25-fold and IL-6 by 99,595-fold. Notably, treatment with simvastatin abolished this CLP-evoked increase in HMBG1 and IL-6 levels in the plasma, suggesting that simvastatin is a potent inhibitor of systemic inflammation in sepsis. Lastly, it was found that simvastatin reduced CLP-induced bacteremia. In conclusion, these novel findings suggest that simvastatin is a powerful regulator of T-cell immune dysfunction in abdominal sepsis. Thus, these protective effects of simvastatin on T-cell functions help to explain the protective effect of statins in patients with sepsis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
-
Shock
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas