IL-10 and TGF-β unbalanced levels in neutrophils contribute to increase inflammatory cytokine expression in childhood obesity.

Abstract

Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW). Our data showed that neutrophils from CO group are capable of antigen recognition and presentation through higher expression of TLR-4 (CD284) and HLA-DR in comparison with neutrophils from NW. On the other hand, neutrophils from CO group are faulty to deliver co-stimulatory signals, through lower expression of co-stimulatory molecules. We showed an increased expression of IL-6, IL-1β, IL-12, and TNF, and decreased expression of IL-8 and IL-10 by neutrophils from CO compared to NW, while TGF-β is equivalently expressed in neutrophils from both groups. Despite this, we observed that TGF-β/inflammatory cytokine ratio was significantly higher than the IL-10/inflammatory cytokine ratio only in CO group. Our analysis showed obesity altering the correlation profile for the expression of co-stimulatory, recognition, and activation molecules, as well as for cytokines by neutrophils, suggesting an association between lower IL-10 expression and inflammation in childhood obesity. The unbalance between the ratio of IL-10 and TGF-β expressions, the IL-10 lower expression, and changes in correlation profile seem to contribute with an inefficient regulation of inflammatory cytokine expression in childhood obesity. However, these changes still not may be considered the sole mechanism that directs inflammation during childhood obesity, once other molecules, pathways, and cells should be evaluated.