Up-Regulation of Interleukin-10 mRNA Expression in Peripheral Leukocytes Predicts Poor Outcome and Diminished Human Leukocyte Antigen-DR Expression on Monocytes in Septic Patients

Abe, Ryuzo; Hirasawa, Hiroyuki; Oda, Shigeto; Sadahiro, Tomohito; Nakamura, Masataka; Watanabe, Eizo; Nakada, Taka-Aki; Hatano, Masahiko; Tokuhisa, Takeshi

doi:10.1016/j.jss.2007.07.009

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Volume 147, Issue 1 , Pages 1-8, 1 June 2008

Up-Regulation of Interleukin-10 mRNA Expression in Peripheral Leukocytes Predicts Poor Outcome and Diminished Human Leukocyte Antigen-DR Expression on Monocytes in Septic Patients

Ryuzo Abe, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
- To whom correspondence and reprint requests should be addressed at Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Ihohana, Chuo, Chiba 260-8670, Japan.
Hiroyuki Hirasawa, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
Shigeto Oda, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
- To whom correspondence and reprint requests should be addressed at Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Ihohana, Chuo, Chiba 260-8670, Japan.
Tomohito Sadahiro, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
Masataka Nakamura, M.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
Eizo Watanabe, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
Taka-Aki Nakada, M.D., Ph.D.
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba University, Chiba, Japan
Masahiko Hatano, M.D., Ph.D.
- Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan
Takeshi Tokuhisa, M.D., Ph.D.
- Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan

Received 13 March 2007 published online 20 August 2007.

Background

None of the parameters can predict the deterioration of sepsis early enough. A new predictor allowing earlier detection of changes in septic patients' condition is indispensable.

Methods

We examined whether cytokine-related mRNA expression in peripheral leukocytes, cytokine blood level, and monocyte human leukocyte antigen (HLA)-DR expression rate could be useful predictors of deterioration of sepsis. Twenty septic patients were enrolled. mRNA expression levels were quantified using real-time reverse transcriptase-polymerase chain reaction and assessed by percent changes during the first 24 h. Cytokine blood levels on admission and day 3 and monocyte HLA-DR expression rate on day 3 were also measured. Correlations between each of these parameters, and between these parameters and outcome were analyzed.

Results

Among seven kinds of cytokines studied, only IL-10 mRNA level showed significant difference between survivors and non-survivors (P < 0.05). Mortality rate of interleukin (IL)-10 mRNA level up-regulated group was significantly higher than that of IL-10 mRNA level down-regulated group (P < 0.05). HLA-DR expression rate in non-survivors were significantly lower than that in survivors (P < 0.05). Although IL-10 blood level on day 3 significantly correlated with HLA-DR expression on day 3(r = 0.54, P < 0.05), IL-10 blood level on admission did not correlate with it. Contrarily, the degree of up-regulation of IL-10 mRNA expression during the first 24 h significantly correlated with the degree of diminished HLA-DR expression on day 3 (r = 0.78, P < 0.001).

Conclusions

Up-regulated IL-10 mRNA expression and diminished HLA-DR expression could be indicators of poor outcome. Furthermore, IL-10 mRNA expression measurement could predict the onset of immunoparalysis indicated by diminished HLA-DR expression earlier than IL-10 blood level measurement, leading to earlier commencement of the treatment.

Key Words: sepsis, cytokine, gene expression, hypercytokinemia, immunoparalysis