Figure 1.

Cytokines play a key role in the orchestration of the immune response: the yin/yang of immunoregulation. This figure depicts the involvement of cytokines, produced by specific cell populations, in the development of Chagas disease. Upon infection, it is important to produce inflammatory cytokines such as IFN-gamma and TNF-alpha, which will activate macrophages to kill the intracellular parasites. However, these cytokines favor the establishment of an inflammatory environment that, if not controlled, may lead to tissue destruction and, thus, the establishment of the cardiac clinical form. On the other hand, if the initial inflammatory environment is controlled by the expression of anti-inflammatory cytokines such as IL-10, this may lead to a balanced response, and the maintenance of the indeterminate clinical form. Several studies have shown that TNF-alpha and IL-10 are mainly produced by monocytes/macrophages, although CD4+ and CD4−CD8−T cells also express these cytokines. IFN-gamma and IL-17 are mainly produced by CD4+ T cells, but CD8+ and CD4−CD8− T cells also express significant percentages of these cytokines. While patients with both clinical forms express inflammatory and anti-inflammatory cytokines, the predominance of an inflammatory environment is observed in cardiac patients, whereas an anti-inflammatory environment is predominantly observed in indeterminate patients.