Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

Figure 1

Relationship between activated immune-inflammatory pathways and oxidative/nitrosative stress (O&NS). CMI involves activation of T cells that produce cytokines such as IFN-γ and IL-2, which activate monocytes/macrophages. Monocytes/macrophages produce IL-1β and IL-12 (that exert a positive feedback loop on T cells), as well as TNF-α, IL-6, and IL-8. Proinflammatory macrophage-derived cytokines (PICs) mediate inflammation enhancing the positive acute phase proteins (APPs), for example, C-reactive protein, and lowering the negative APPs, for example, albumin. The counterinflammatory response syndrome (CARS) tends to dampen the acute inflammatory response producing IL-4 and IL-10 (responsible for decreasing TNF-α, IL-1, IL-6, and IL-8) and the antagonists to TNF-α and IL-1 receptors (IL-1RA), which inactivate the cytokine or block the receptors. Immune inflammation and O&NS influence each other. Inflammatory and CMI responses are accompanied by increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) while oxidative stress maintains inflammation mainly through the activation of toll-like receptors (TLRs). Damaged macromolecules released during condition of oxidative stress can activate TLRs which produce an inflammatory response whose key mediators are IL-1, IL6, and TNF-α. CMI: cell-mediated immune; IL-6: interleukin-6; IL-1β: interleukin-1β; IL-12: interleukin-12; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ; APPs: acute phase proteins; TLRs: toll-like receptors.