Brain, behavior, and immunity
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Brain Behav. Immun. · Mar 2015
Total and differential white blood cell counts, high-sensitivity C-reactive protein, and cardiovascular risk in non-affective psychoses.
Schizophrenia is associated with increased cardiovascular disease morbidity and mortality. Schizophrenia is also associated with immune and inflammatory abnormalities, including aberrant blood levels of lymphocytes, cytokines and high-sensitivity C-reactive protein (hsCRP). The purpose of this study is to investigate the relationship between total and differential white blood cell (WBC) counts, hsCRP, and indices of cardiovascular disease risk in patients with schizophrenia and related non-affective psychoses. 108 inpatients and outpatients age 18-70 with non-affective psychoses and 44 controls participated in this cross-sectional study. ⋯ In binary logistic regression analyses, total WBC count was a significant predictor of an elevated 10-year estimated risk of myocardial infarction and cardiovascular disease in subjects with non-affective psychosis (p⩽0.03 for each). Associations between total and differential WBC counts and cardiovascular disease risk indices were stronger in males than females with non-affective psychosis. Our findings provide further evidence that measurement of total and differential WBC counts may be germane to the clinical care of patients with schizophrenia and related disorders, and support an association between inflammation and cardiovascular disease risk in these patients.
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Brain Behav. Immun. · Mar 2015
Randomized Controlled Trial Observational StudyVariable neuroendocrine-immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury.
Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). ⋯ Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune dysfunction differs between cortisol TRAJ groups. These results present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.
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Brain Behav. Immun. · Mar 2015
Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.
Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. ⋯ Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.
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Brain Behav. Immun. · Mar 2015
Alcohol-induced sedation and synergistic interactions between alcohol and morphine: a key mechanistic role for Toll-like receptors and MyD88-dependent signaling.
Increasing evidence demonstrates induction of proinflammatory Toll-like receptor (TLR) 2 and TLR4 signaling by morphine and, TLR4 signaling by alcohol; thus indicating a common site of drug action and a potential novel innate immune-dependent hypothesis for opioid and alcohol drug interactions. Hence, the current study aimed to assess the role of TLR2, TLR4, MyD88 (as a critical TLR-signaling participant), NF-κB, Interleukin-1β (IL-1β; as a downstream proinflammatory effector molecule) and the μ opioid receptor (MOR; as a classical site for morphine action) in acute alcohol-induced sedation (4.5g/kg) and alcohol (2.5g/kg) interaction with morphine (5mg/kg) by assessing the loss of righting reflex (LORR) as a measure of sedation. ⋯ In contrast, the interaction between morphine and alcohol was found to be MOR-, NF-κB-, TLR2- and MyD88-dependent, but did not involve TLR4 or Interleukin-1β. Morphine-alcohol interactions caused acute elevations in microglial cell counts and NF-κB-p65 positive cells in the motor cortex in concordance with wild-type and TLR2 deficient mouse behavioral data, implicating neuroimmunopharmacological signaling as a pivotal mechanism in this clinically problematic drug-drug interaction.
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Brain Behav. Immun. · Mar 2015
ReviewRole of the immune system in HIV-associated neuroinflammation and neurocognitive implications.
Individuals living with HIV who are optimally treated with combination antiretroviral therapy (cART) can now lead an extended life. In spite of this remarkable survival benefit from viral suppression achieved by cART in peripheral blood, the rate of mild to moderate cognitive impairment remains high. A cognitive decline that includes impairments in attention, learning and executive function is accompanied by increased rates of mood disorders that together adversely impact the daily life of those with chronic HIV infection. ⋯ Cytokines, which are elevated in the blood of patients with HIV infection, may also contribute to brain inflammation by entering the brain from the blood. Host factors such as aging and co-morbid conditions such as cytomegalovirus co-infection and vascular pathology are important factors that affect the HIV-host immune interactions in HAND pathogenesis. By these diverse mechanisms, HIV-1 induces a neuroinflammatory response that is likely to be a major contributor to the cognitive and behavior changes seen in HIV infection.