Low doses of E2 enhance the production of proinflammatory cytokines (IL-1, IL-6, TNF- α) and T helper cell type 1 (Th1) responses, while high or sustained E2 concentrations are associated with an increased susceptibility to infections [28], reduced proinflammatory cytokine production and enhanced Th2 responses and humoral immunity [23,29]. The gene discussed is TNF; the disease is infection.