Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes

The components of the innate immune system. Sentinel cells such as the macrophage detect potential environmental threats from infection, chemicals, and foods by PRRs that activate signaling pathways and release proinflammatory cytokines (IL-6 and TNF-α). Known PRRs include TLR-4, which senses bacterial LPS and the receptor for AGEs. Cytokines stimulate acute-phase protein production from the liver and also act on the brain to release adrenocorticotrophic hormone (and thereby cortisol from the adrenal gland) and activate the sympathetic nervous system with the release of catecholamines. Psychological stress can cause an acute-phase response via innervation of cytokine-producing cells and via activation of the sympathetic nervous system and adrenergic receptors on macrophages. Central cytokine-induced “sickness behavior” includes lethargy, sleep changes, and depression. The innate immune system also controls the adaptive (acquired) immune system via costimulatory molecule expression that is necessary for antigen presentation. SAA, serum amyloid A.