The correlation between Jun N-terminal kinase pathway-associated phosphatase and Th1 cell or Th17 cell in sepsis and their potential roles in clinical sepsis management

Abstract

Background: We aimed to investigate the association between Jun N-terminal kinase (JNK) pathway-associated phosphatase (JKAP) and T helper type 1 (Th1) cell or Th17 cell, and their clinical values in sepsis patients.

Methods: Totally 125 sepsis patients and 100 healthy subjects as controls were included. Peripheral blood was extracted from each sepsis patient and each control, then serum and peripheral blood mononuclear cell (PBMC) were separated. JKAP and inflammatory cytokines were detected in serum by ELISA; Th1 cell or Th17 cell proportion was detected in PBMC using flow cytometry.

Results: JKAP level was downregulated while Th1 and Th17 cell proportions were upregulated in sepsis patients compared with controls. JKAP level negatively correlated with Th1 cell proportion in sepsis patients and controls, while was only negatively associated with Th17 cell proportion in sepsis patients but not in controls. In sepsis patients, JKAP level negatively associated with TNF-α, IL-1β, and IL-17 expressions. Meanwhile, JKAP level negatively but Th17 cell proportion positively correlated with acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores; however, Th1 cell proportion only positively associated with APACHE II score but not SOFA score. Additionally, JKAP level was reduced, while Th1 and Th17 cell proportions were increased in septic deaths compared with survivors. Multivariate logistic regression model disclosed that JKAP level and Th17 cell proportion independently predicted 28-day mortality.

Conclusion: Blood JKAP correlates with decreased Th1 and Th17 cells, also associates with reduced inflammatory cytokines, disease severity, and favorable outcome in sepsis patients.

Keywords: Inflammatory cytokines; Jun N-terminal kinase (JNK) pathway-associated phosphatase; Mortality; Sepsis; T helper type 1; T helper type 17.

Fig. 1

Comparisons of JKAP level, Th1, and Th17 cell proportions between sepsis patients and controls. The comparisons of JKAP level (a), Th1 cell proportion (b), and Th17 cell proportion (c) between sepsis patients and controls. The bars stood for 1st quartile, median, and 3rd quartile of JKAP level, Th1 cell proportion, or Th17 cell proportion, respectively. JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; Th1, T helper type 1; Th17, T helper type 17

Fig. 2

Analysis of association between JKAP level and Th1 or Th17 cell proportion. The association of JKAP level with Th1 cell proportion (a) or Th17 cell proportion (b) in sepsis patients, the association of JKAP level with Th1 cell proportion (c) or Th17 cell proportion (d) in controls. JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; Th1, T helper type 1; Th17, T helper type 17

Fig. 3

Analysis of association between JKAP level and inflammatory cytokines expressions in sepsis patients. The association of JKAP level with TNF-α (a), IL-1β (b), or IL-17 (c) expression in sepsis patients. JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; IL-17, interleukin-17

Fig. 4

Analysis of association of JKAP level, Th1, or Th17 cell proportion with APACHE II or SOFA score in sepsis patients. Association between JKAP level (A), Th1 cell proportion (B), Th17 cell proportion (C) and APACHE II score, association between JKAP level (D), Th1 cell proportion (E), Th17 cell proportion (F) and SOFA score in sepsis patients. JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; Th1, T helper type 1; Th17, T helper type 17; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment

Fig. 5

Comparison of JKAP level and Th1 or Th17 cell proportion in deaths and survivors. The comparison of JKAP level (a), Th1 cell proportion (b), or Th17 cell proportion (c) between deaths and survivors in sepsis patients. JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; Th1, T helper type 1; Th17, T helper type 17

Fig. 6

ROC analysis of JKAP level, Th1 or Th17 cell proportion, APACHE II score, and SOFA score for predicting 28-day mortality. ROC, receiver operating characteristic; JKAP, Jun N-terminal kinase (JNK) pathway-associated phosphatase; Th1, T helper type 1; Th17, T helper type 17; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment; AUC, area under curve; 95% CI, 95% confidence interval

Fig. 7

ROC analysis of the combination of independent predictive factors for 28-day mortality in sepsis patients. Dot in black stood for the best cut-off point. ROC, receiver operating characteristic; AUC, area under curve; 95% CI, 95% confidence interval