Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

Background: the pleiotropic pro-inflammatory cytokine interleukin (il)-18 has been proposed to play a role in schizophrenia,since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients.methods: we analyzed 77 patients with schizophrenia diagnosis (scz) and 77 healthy control subjects (hc) for serum concentration of both il-18 and its natural inhibitor,the il-18 binding protein (il-18bp).results: we confirmed that serum levels of total il-18 are significantly increased in scz,as compared to hc. however,due to a highly significant increase in levels of circulating il-18bp in scz,as compared to hc,the levels of free,bioactive il-18 are not significantly different between the two groups. in addition,the relationships between the levels of il-18 and its inhibitor,as well as between the two molecules and age appear dissimilar for scz and hc. in particular,the elevated levels of il-18bp,likely a consequence of the body's attempt to counteract the early prominent inflammation which characterizes schizophrenia,are maintained in earlier and later stages of the disease. however,the il-18bp elevation appears ineffective to balance the il-18 system in younger scz patients,while in older patients the levels of circulating bioactive il-18 are comparable to those of hc,if not lower.conclusions: in conclusion,these findings indicate that the il-18 system is perturbed in schizophrenia,supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease. © 2012 palladino et al.; licensee biomed central ltd.