Clinical Implication of Serum TNF-$\alpha$ and IL-1$\beta$ Measurement in Patients with Sepsis

패혈증환자에서 혈청 TNF-$\alpha$ 및 IL-1$\beta$

  • Kim, Jae-Yeol ;
  • Choi, Hyung-Seok (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Lee, Choon-Taek (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Kim, Young-Whan (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Han, Sung-Koo (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Min, Kyung-Up (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Kim, Yoo-Young (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Shim, Young-Soo (Department of Internal Medicine & Lung Institute, Seoul National University) ;
  • Yoo, Chul-Gyu (Department of Internal Medicine & Lung Institute, Seoul National University)
  • 김재열 (중앙대학교 의과대학 내과학교실) ;
  • ;
  • 이춘택 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 김영환 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 한성구 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 민경업 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 김유경 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 심영수 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소) ;
  • 유철규 (서울대학교 의과대학 내과학교실 및 의학연구원 폐 연구소)
  • Published : 2000.08.30

Abstract

Background : It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-$\alpha$ and IL-1$\beta$. However, there is an alteration in the macrophages' responsiveness when they are challenged with repeated bouts of endotoxin, termed "endotoxin tolerance" which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. Methods : Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE II score. Peripheral blood monocytes were isolated from the patients and diluted to $1{\times}10^5$ well. After stimulation with endotoxin (LPS of E. coli O114 : B4, 100 ng/ml), they were incubated at $37^{\circ}C$ in 5% $CO_2$ incubator for 24 hours. Supernatant was collected for the measurement of TNF-$\alpha$ and IL-1$\beta$ with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. Results : The APACHE II score (mean$\pm$SD) of the patients at the time of blood sampling was 12.2$\pm$5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods (10 cases), gram positive cocci (6 cases) with two cases of mixed infection. Serum TNF-$\alpha$ could be measured in 4 cases with 29.9$\pm$27.7 pg/ml. Serum IL-1$\beta$was measurable in only one patient. The TNF-$\alpha$ level of supernatant of cultured peripheral blood monocytes was 2,703$\pm$2,066 pg/ml in patients and 2,102$\pm$1914 pg/ml in controls. The IL-1$\beta$level of supernatant was 884$\pm$1,050 pg/ml in patients and 575$\pm$558 pg/ml in controls. There was no difference of TNF-$\alpha$ and IL-1$\beta$ level between patients and controls. Conclusion : We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

Acknowledgement

Supported by : 서울대학교병원