ABSTRACT
Objective To investigate the change of expression of toll like receptor 4( TLR4)on peripheral blood monouclear cells( PBMC) and clinical significance of sepsis acute kidney injury( AKI) patients. Methods ICU admission diagnosis of sepsis patients from May 2012 to December 2013 in the Zhongxin Hospital of Handan were diagnosed AKI according to the KDIGO guidelines of 2012 and were divided into AKI group and non AKI. Meanwhile,patients with AKI were also divided into group Ⅰ(KDIGO Ⅰ period);group Ⅱ( KDIGO Ⅱ period)and group Ⅲ( KDIGO Ⅲ period)according to the AKI stages. Thirty cases health patients were elected as the control group. The expression levels of TLR4,human leucocyte antigen(HLA-DR)on PBMC with of sepsis patients were detected with the flow cytometry. The levels of interleukin-6(IL-6) and interleukin-10(IL-10)in serum were detected by enzyme linked immunosorbent assay(ELISA). The length of ICU stay,ICU mortality and the APACHE Ⅱ in 24 h were recorded. Results (1)The expression levels of TLR4 in sepsis AKI patients was(34. 45 ± 9. 54),higher than that in patients without AKI and control group ((26. 29 ± 6. 76,10. 72 ± 8. 82;F = 55. 351,P < 0. 01). The expression of TLR4 in sepsis AKI patients was higher than sepsis patients without AKI(P < 0. 05). There was significant difference among sub AKI groups in terms of TLR4(F = 13. 235,P < 0. 01),and it significantly lower in group Ⅲ among three groups.(P < 0. 05 or P < 0. 01).(2)The levels of IL-6,IL-10 in sepsis AKI group were(565. 81 ± 106. 27)ng/ L,(76. 78 ± 12. 33) ng/ L,higher than those in non AKI group and control group((321. 85 ± 76. 62)ng/ L,(38. 53 ± 9. 93)ng/ L;(84. 36 ± 36. 91)ng/ L,(17. 53 ± 6. 08)ng/ L;F = 264. 962,254. 398,P < 0. 01). While,the levels of IL-6,IL-10 in sepsis AKI group were higher than those in non AKI group(P < 0. 05). However,there was no significant difference among three sub AKI groups in terms of IL-6 levels. The IL-10 level in group Ⅲ was highest among three sub AKI groups(P < 0. 05).(3)ICU mortality in sepsis AKI group and non AKI group were 34. 8% and 14. 8%(χ2 = 3. 410,P = 0. 065). Meanwhile,ICU mortality in three sub-AKI groups were 20. 0% ,33. 3% , 57. 1% ,and there was no significant difference(P = 0. 120). The length of ICU stay in non ALI group was(4. 14 ± 1. 65)d,shorter than that in AKI group(10. 52 ± 3. 70)d;t = 8. 201,P = 0. 000). Meanwhile,The length of ICU stay in three sub-AKI groups were(8. 93 ± 1. 81)d,(10. 17 ± 2. 31)d,(14. 71. ± 2. 81)d,and the difference was significant(F = 19. 052,P = 0. 000). APACHE-Ⅱ in three sub-AKI groups Ⅰ,group Ⅱ,groupⅢ were 20. 20 ± 4. 07,21. 00 ± 3. 16,30. 57 ± 2. 44 respectively and the difference was significant(P < 0. 05 or P < 0. 01). Conclusion TLR4 mediated inflammation is involved in the sepsis AKI process. Because the damage degree of AKI is aggravating,immune factors also participate in the development of AKI. And with the decrease of HLA-DR,the probability of RRT increases.
ABSTRACT
Objective To investigate the expression of Toll-like receptor 4 (TLR4) of peripheral blood mononuclear cell (PBMC) in the different prognosis of patients with severe sepsis and its relation with endotoxin-tolerant.Methods Thirty-five patients with severe sepsis (severe sepsis group) and 15 healthy volunteers (control group),respectively stayed in ICU 24 h and physical examination in the day measured TLR4 expression of PBMC by flow cytometry and measured the serum of tumor necrosis factor (TNF)-α and interleukin (IL)-10 by enzyme-linked immunosorbentassay.Simultaneous separation of peripheral blood of PBMC,addition of 40 μ g/ml lipopolysaccharide (LPS) cultured for 24 h,and TLR4 expression of PBMC was measured in the same manner and the culture supernatant of TNF-α and IL-10.Results Thirty-five patients with severe sepsis survivor 25 cases (survivor group) and death 10 cases (death group),28 d death rate was 28.6％ (10/35).The TLR4 expression of PBMC in severe sepsis group was significantly lower than that in control group [(11.09 ± 8.90) MFI vs.(33.72 ± 12.59) MFI,P ＜ 0.01],the serum TNF-α and IL-10 in severe sepsis group were significantly higher than those in control group [(96.66 ± 45.33) ng/L vs.(2.53 ± 1.21) ng/L,(149.79 ± 67.15) ng/L vs.(34.56 ± 19.08) ng/L,P ＜ 0.01].There was no significant difference in TLR4 expression of PBMC between survivor group and death group (P ＞ 0.05).The TLR4 expression of PBMC in control group after LPS stimulation was significantly higher than that before LPS stimulation [(50.22 ± 19.23) MFI vs.(33.72 ± 12.59) MFI,P ＜ 0.05],survivor group and death group after LPS stimulation were significantly lower than those before LPS stimulation [(4.55 ± 2.30) MFI vs.(11.21 ±7.92) M FI and (5.46 ± 3.44) M FI vs.(10.15 ± 9.70) MFI,P ＜ 0.01].The culture supernatant of TNF-α,IL-10 in survivor group and death group were significantly lower than those in control group [(22.34 ± 8.27)and (19.49 ±5.35) ng/L vs.(88.70 ±34.21) ng/L,(54.29 ±32.89) and (98.04 ±40.26) ng/L vs.(146.56 ± 52.18) ng/L,P ＜ 0.01],but the culture supernatant of IL-10 in death group was significantly higher than that in survivor group (P ＜ 0.05).Conclusion Different prognosis of patients with severe sepsis have endotoxin tolerance and different inflammatory cytokine secretion abifity.