Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

Abstract

Purpose:We aim to identify Th1 and Th2 cell clusters in young subjects, including their clinical and metabolic characteristics and the Th1/Th2 balance. Patients and Methods: A total of 100 participants were included. The frequencies of Th1 and Th2 cells in peripheral blood were determined by flow cytometry. Serum C-reactive protein was measured using a turbidimetric assay, and insulin levels were quantified with an enzyme-linked immunosorbent assay. Circulating cytokine levels were analyzed using a multiplex system. Results: A cluster analysis was performed to determine the Th1/Th2 balance in a group of young people, and 3 clusters were formed with the following characteristics: 1) subjects with a higher prevalence of hyperglycemia (38%), dyslipidemia (38-75%), and insulin resistance (50%), as well as a higher percentage of Th1 cells and Th1/Th2 ratio, including elevated IFN-ɣ levels; 2) subjects with a lower prevalence of hyperglycemia (23%) and insulin resistance (15.4%), but a higher prevalence of dyslipidemia (8-85%) with a predominance of Th2 cells, and lower Th1/Th2 ratio; 3) subjects with a lower prevalence of hyperglycemia (6%), insulin resistance (41%), and dyslipidemia (10-63%), as well as a balance of Th1 and Th2 cells and lower Th1/Th2 ratio, including low IFN-ɣ levels. Positive correlations between Th1 cells with IFN-γ, IL-12, and IL-1β and between Th2 cells with IFN-γ, IL-2, and IL-4 were found (p < 0.05). A significant increase in Th1 cells was observed in the presence of hyperglycemia and high LDL-C levels, as well as increased Th2 cells in the absence of abdominal obesity and high blood pressure, including low HDL-C levels. The Th1/Th2 ratio was higher in the group with high cardiometabolic risk (p = 0.03). Conclusion: Th1/Th2 balance is related to metabolic abnormalities that may occur in young population, and thus the timely identification of different phenotypes may help predict an increased cardiometabolic risk.

The Interplay of Obesity, Dyslipidemia and Immune Dysfunction: A Brief Overview on Pathophysiology, Animal Models, and Nutritional Modulation

“…Higher proportions of CD4+ Th cells in PBMC were also observed in obese subjects (BMI > 35) compared to lean controls ( 33 ). In addition to obesity, factors such as hyperglycemia, dyslipidemia and insulin resistance have been shown to further modulate circulating T cell subtypes by increasing the ratio of Th1 to Th2 cells ( 34 ). Recent findings from our group also demonstrated that hyperglycemia in obesity and type 2 diabetes leads to an increased proportion of activated Th cells (expressing CD278), cytotoxic T cells as well as inflammatory monocytes (CD14+CRTh2+) in PBMC compared to individuals with obesity that are metabolically healthy ( 4 ).…”

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

“…The meta-analysis showed there was a higher percentage of Th2 cells in patients than HCs (SMD = 0.62; 95% CI = 0.03, 1.20; p = 0.04; n = 8; Figure 2 ). Sensitivity analysis that excluded the Yong Wang study ( Wang et al, 2006 ) and the Yanni Jiang study ( Matia-Garcia et al, 2021 ) reduced the heterogeneity of these results (I 2 = 2.22%; Supplementary Figure S2 ), and the percentage of Th2 cells remained higher in patients than HCs (SMD = 0.29; 95% CI = 0.03, 0.56; p = 0.03; n = 6).…”

“…Although many studies have examined the levels of Th1 and Th2 cells in patients with SLE, many of these results are discordant ( Viallard et al, 1999 ; Amit et al, 2000 ; Li et al, 2002a ; Oster et al, 2019 ). Thus, examination of changes in the levels of Th1 and Th2 cells during SLE is an active area of research ( Matia-Garcia et al, 2021 ).…”

COVID‐19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances

“…In general, there is an upregulation of both Th1 and Th17 profiles, including their characteristic cytokines, while Th2 and Treg profiles and their cytokines are downregulated in obesity. 122 , 123 , 124 , 125 The Treg/Th17 ratio is decreased in obesity, and this is related to metabolic health. 126 , 127 Severe COVID‐19, in turn, provokes dampened Th1 and Treg responses, while promoting the Th17 profile.…”

“…Despite these results, an important feature that was largely overlooked in the studies is the further characterization of the subsets of lymphocytes beyond CD4 + T cells. In general, there is an upregulation of both Th1 and Th17 profiles, including their characteristic cytokines, while Th2 and Treg profiles and their cytokines are downregulated in obesity 122–125 . The Treg/Th17 ratio is decreased in obesity, and this is related to metabolic health 126,127 .…”