The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders - relation to drug treatment

Figures & data

Table I. Components of the unspecific “innate” and the specific “adaptive” immune systems in humans.

Table II. Cytokines of the polarized immune response. IL, interleukin; IFN, interferon; TNF, tumor necrosis factor.

Figure 1. Neuroimmune interactions of kynurenine intermediates. Metabolism of tryptophan via the kynurenine pathway leads to several neuroactive intermediates; kynurenic acid (synthesised by kynurenine aminotransferase, KAT) has neuroprotective properties through antagonism at the N-methyl-Daspartate (NMDA) receptor. Quinolinic acid (QUIN), in contrast, is an NMDA receptor agonist. Both 3-hydroxykynurenine (3OH-kynurenine)and QUIN can induce neurodegeneration and apoptosis through induction of excitotoxicity and generation of neurotoxic radicals, respectively. Activity of the key enzyme of the kynurenine pathway, indoleamine 2,3-dioxygenase (IDO), and of the 3-OH-kynurenine forming enzyme kynurenine monoxygenase (KMO) is induced by proinflammatory cytokines like interferon-γ (IFN-γ) and inhibited by anti-inflammatory cytokines like interleukin-4 (IL-4). Serotonin is normally degraded to 5-hydroxyindoleacetic acid (5-HIAA), but the indole ring of serotonin can also be cleaved by IDO. (blue arrows = activation; red arrows = inhibition).