Cytokine effects on cortical neuron MAP-2 immunoreactivity: Implications for schizophrenia

Background: Cytokines demonstrate diverse actions in the brain and modulate systemic and central nervous system (CNS) responses to injury, infection, and inflammation. Cytokines in the CNS are elevated during infection and is chemia, two neurodevelopmental insults associated with increased schizophre nia risk. We hypothesize that cytokine-mediated neuronal injury during deve lopment may contribute to schizophrenia pathophysiology, causing subtle alt erations in neuronal number and density. Methods: We examined cytokine regulation of neuronal number in embryonic da y 18 rat cortical cultures using MAP-2 immunohistochemistry. Mixed cultures derived from frontal cortex were fixed and stained after 48-hour exposure to the proinflammatory interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) , or tumor necrosis factor-alpha (TNF-alpha; 0, 10, 100, or 1000 units/mL). Results: IL-1 beta (maximum effect 35%) and IL-6 (maximum effect 29%) produ ced dose-dependent decreases in the number of cells (neurons) immunoreactiv e for MAP-2 antibody, suggesting decreased neuronal survival. TNF-alpha als o tended to decrease MAP-2 immunostaining at the highest dose tested. Conclusions: Our data suggest a role for cytokines in the modulation of neu ronal survival during neurodevelopment, a finding potentially relevant to s chizophrenia pathophysiology. If cytokine-mediated neuronal injury proves t o be a common response to gestational insults associated with increased sch izophrenia risk, the pharmacologic modulation of these molecules may have c linical utility. (C) 2001 Society of Biological Psychiatry.