Abstract Body

There is a great variety of immune alterations observed in the peripheral blood or cerebrospinal fluid of patients with schizophrenia that include elevated levels of pro-inflammatory cytokines, specific and non-specific antibodies, components of complement cascade, acute phase proteins as well as shifts in the subpopulations of lymphocytes. There is also a growing literature suggesting that up-regulation of immune response is related to alterations of kynurenine pathway function and together are involved in pathogenesis of schizophrenia.

Kynurenic acid (KynA) is a neuroactive metabolite of tryptophan formed in the brain and in the periphery, known to block ionotropic glutamate receptors and α7 nicotinic receptors, and to act as a ligand of G protein-coupled GPR35 receptors and human aryl hydrocarbon (AHR) receptors. Since KynA is the only known endogenous NMDA receptor antagonist, psychosis and schizophrenia were postulated to be caused by the effect of elevated KynA on glutamatergic and ultimately, dopaminergic neurotransmission

Central level of KynA may increase in the course of inflammation, which is consistent with the inflammatory hypothesis of schizophrenia. The reported increase in KynA in schizophrenia and psychosis may originate from inflammation-driven increases in KYN (kynurenine). As in the case of mood disorders, there is evidence that inflammation may play a mechanistic role in schizophrenia and PET studies have reported increased microglial activation in patients with schizophrenia

Alterations of immune response and disturbed functioning of kynurenine pathway may lead to disproportion between neuroprotective and neurotoxic mechanisms in the brain.