Cytokine concentration in peripheral blood of patients with childhood obesity

Abstract

Introduction: Obesity is marked by chronic inflammation, with research showing notable changes in cytokines. However, systematic investigations into cytokine level changes are still lacking. This study compared the concentrations of various cytokines in the peripheral blood of healthy controls and obese children.

Methods: Peripheral blood samples from test cohort including 5 healthy children and 5 obesity children were used to evaluate concentration levels of 48 inflammatory cytokines by Bio-Plex assay. Diet-induced obese (DIO) mice used to assess whether there were significant differences in the expression of MIP-1b, PDGF-BB. Peripheral blood samples from validation cohort including 44 healthy children and 44 obesity children were used to evaluate concentration levels of MIP-1b, PDGF-BB, IP-10, IL-6, IL-9 and TNF-β.

Results: In the Bio-Plex assay, there were significant differences in MIP-1b and PDGF-BB levels between healthy and obesity children. Additionally, IP-10, IL-6, IL-9, and TNF-β exhibited a trend of difference between the two groups. However, no significant differences in MIP-1b and PDGF-BB levels were observed between control and DIO mice. Notably, we found that IL-6 exhibited a significant concentration difference between the serum of healthy and obesity children, suggesting the IL-6 may play a key role in the inflammatory response associated with obesity.

Discussion: In summary, our study emphasizes the importance of IL-6 and other cytokines in childhood obesity research and suggests that future investigations should further explore the specific roles of these cytokines in the pathophysiological states associated with obesity, aiming to provide new strategies for the prevention and treatment of obesity.

Keywords: IL-6; childhood obesity; cytokine concentration; inflammation; peripheral blood.

Figure 1

The concentrations of cytokines in patients with childhood obesity. (A) Heatmap of differentially expressed 41 serum multi-cytokines between participants with childhood obesity and healthy controls using Bio-Plex assay. (B) Correlation heatmap of 41 serum cytokines and BMI in healthy controls and children with obesity. (C-H) Concentrations of MIP-1b (C), PDGF-BB (D), IP-10 (E), IL-6 (F), IL-9 (G) and TNF-β (H) in the peripheral blood of the test cohort. (*: P<0.05; **: P<0.01).

Figure 2

The concentrations of cytokines in the serum of control and obesity mice. (A) Representative photo in C57BL/6J mice fed standard diet (control) or high-fat-diet (obesity) for 19 weeks. (B) Growth curve in body weight of standard diet (control) or high-fat-diet fed (obesity) C57BL/6J mice. (C) Subcutaneous and epididymal adipose tissue of standard diet or high-fat-diet fed C57BL/6J mice. (D) Body fat percentage of control and obesity mice. (E) Lees’ index of control and obesity mice. (F-H) Blood lipid metabolism markers levels of control and obesity mice. (I, J) Concentrations of MIP-1b (I), PDGF-BB (J) in the serum of control and obesity mice. (ns: P>0.05, not significant; **: P<0.01; ***: P<0.001).

Figure 3

The concentrations of cytokines in patients with childhood obesity of validation cohorts. (A-F) Concentrations of MIP-1b (A), PDGF-BB (B), IP-10 (C), IL-6 (D), IL-9 (E) and TNF-β (F) in the peripheral blood of the validation cohorts. (G) Correlation heatmap of HDL/LDL and individual cytokines (MIP-1b, PDGF-BB, IP-10, IL-6, IL-9 and TNF-β). (H) The correlation index and P value of HDL/LDL and individual cytokines (MIP-1b, PDGF-BB, IP-10, IL-6, IL-9 and TNF-β). (ns: P>0.05, not significant; *: P<0.05; **: P<0.01; ***: P<0.001).

Figure 4

Diagnostic outcomes for serum cytokines in the diagnosis of childhood obesity. (A-C) ROC curve for IL-6 (A), IP-10 (B) and PDGF-BB (C) for patients with childhood obesity versus controls in the validation cohorts. (D) ROC curve for both IL-6 and IP-10 for patients with childhood obesity versus controls in the validation cohorts. (E) ROC curve for both IL-6 and PDGF-BB for patients with childhood obesity versus controls in the validation cohorts. (F) ROC curve for combine IL-6, IP-10 and PDGF-BB for patients with childhood obesity versus controls in the validation cohorts. (G) Results for measurement of serum IL-6, IP-10, PDGF-BB, or both in the diagnosis of childhood obesity, AUC (area under curve); PPV (positive predictive value); NPV (negative predictive value); PLR (positive likelihood ratio); NLR (negative likelihood ratio).