Heme oxygenase-1 in blood and saliva during acute psychosis: A pilot study.

Despite the extensive prevalence of psychosis and schizophrenia spectrum disorders, their biological underpinnings remain largely unexplained. Recently, the overproduction of heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme, was associated with oxidative stress and a neurologic phenotype similar to schizophrenia in transgenic mice. We sought to evaluate, by comparing patients experiencing an acute psychotic episode, and age/sex-matched healthy control participants, whether there was an association between HO-1 overexpression and psychosis. This cross-sectional pilot study included 16 patients and 17 control participants. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were used to quantify HO-1 expression in blood and saliva. Four psychiatric questionnaires were used to measure psychiatric symptoms in participants. Higher levels of salivary HO-1 expression were detected in patients experiencing an acute psychotic episode when compared to control participants (84.01 vs. 61.26 ng/ml, p = 0.026), but plasma and lymphocyte HO-1 expression did not significantly differ between groups. Overexpression of HO-1 in saliva specimens was also positively associated with psychiatric symptom severity and disability. The overexpression of HO-1 in the saliva of patients with psychosis suggests that it may serve as a potential biomarker for this symptom which should be explored in larger clinical trials.

The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells.

We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31. Other groups were sacrificed on days 3, 5, 7, 14, 21 and 31 days post transplant to record the total number of cells in the spleens and their phenotypes. Neutrophils were isolated from the spleens of mice transplanted with B6 and BALB/c cells on days 7 and 14. Daily body weight demonstrated a transient drop in the syngeneic transplants on day 2 but a much greater drop with its nadir at day 7 and never fully recovering through 31 days. CD8/CD4 T lymphocytes peaked in the spleen on day 5 and were followed on day 7 by GR-I cells in all of the allogeneic transplants. In syngeneic transplants this early rise in lymphocytes did not occur and GR-1 cells peaked on day 14. Highly purified neutrophils were isolated in two separate experiments from the spleens on days 7 and 14 post transplant. In both experiments day 7 allogeneic neutrophils expressed significantly elevated levels of Interleukin-21 (IL-21) mRNA whereas the day 7 and 14 syngeneic cells expressed lower but significant levels of TNFα. Intracellular IL-21 was demonstrated in the allogeneic neutrophils on day 7 before and after in vitro stimulation. In conclusion Purified neutrophils isolated from the spleen on day 7, the early peak of allogeneic transplantation a GVHD, express high levels of IL-21 message and intracellular IL-21.