In the last decade an increasing body of research has focussed on the potential role of inflammation in the onset of psychiatric disorders. Although the association between inflammation and depression appears now widely acknowledged, mixed findings have been reported in psychosis leaving the pathophysiological role of inflammation in psychosis still unclear. This paper aims to review studies focussing on inflammation in first-episode psychosis, in order to avoid the possible confounding effects of the long duration of illness and chronic treatment with psychotropic medications. Increased levels of IL-6, TNF-α and IL-1β are the most consistent findings from the studies conducted in first-episode psychosis patients. Mixed findings on other cytokines could be partly due to the different methodologies of the studies reviewed. The findings on the association between inflammatory markers and clinical symptoms and physical health, as well as on the effect of antipsychotic medications on inflammation at the onset of psychosis are also reviewed and discussed. The increased inflammation at onset of psychosis as well as in other psychiatric conditions, such as depression, suggests the presence of biological abnormalities which play a pathophysiological role across different diagnostic categories. Future research should test if increased inflammation could be used for the development of biomarkers, as well as as a potential therapeutic target for different subsamples of patients independently of their diagnostic category.

Background/Aims: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. Methods: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. Results and Conclusion: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring.

Objectives: Experimental evidences indicate that leptin is involved in the neuroinflammatory process sustaining multiple sclerosis (MS). However, the relationship between leptin and body fat, as assessed by body mass index (BMI), in MS was not previously evaluated. It was the aim of this study to compare serum leptin levels between patients with MS and healthy controls and to evaluate the possible relationship between circulating leptin levels and disease severity. Patients and Methods: Eighty-four MS patients and 57 sex-matched healthy volunteers were enrolled. Serum leptin levels were measured in all patients and controls. MS patients were stratified in 3 groups according to their degree of disability as assessed by the Expanded Disability Status Scale (EDSS). Patients were classified as having low (33 patients with an EDSS score <1.5), intermediate (28 patients with an EDSS score from 2 to 3) and high disability (23 patients with an EDSS score ≥3.5). Results: No significant differences in serum leptin levels and BMI were observed between patients and controls. In patients with MS, serum leptin levels were significantly correlated with BMI in those patients with low (R² = 0.363; p < 0.001) and intermediate disability (R² = 0.408; p < 0.001), but not in patients with a higher disability score (R² = 0.064; p = 0.256). Conclusion: BMI, the major determinant of leptin level in physiological conditions, has a minor role in determining the serum levels of leptin in MS patients with a high EDSS score. Future longitudinal studies will be required in order to provide further insights into the regulation of leptin secretion in patients with MS.

Objectives: Lipopolysaccharide (LPS), an endotoxin that originates from the cell wall of Gram-negative bacteria, activates the immune system to release proinflammatory cytokines and to induce sickness behavior. The present study sought to characterize the time-dependent effects of LPS on fever, body weight, and food and water consumption in female virgin and lactating rats exposed to an LPS dose previously reported to induce sickness behavior in pregnant female rats. Methods: Virgin female Wistar rats in the estrous phase and lactating female Wistar rats on the third day of lactation received 100 µg/kg LPS or saline solution. Tympanic temperature, body weight, and food and water consumption were assessed 0, 2, 24, 48, 72, 96, and 120 h after treatment. Results: In lactating female rats, tympanic temperature was attenuated compared with virgin females. Food consumption and body weight gain in both groups decreased, but lactating rats consumed more food than virgin rats. Water consumption increased at different time points. Conclusion: LPS exposure induced several signs of sickness behavior, including decreases in food consumption and body weight gain, and induced adipsia in both virgin and lactating female rats. Because the time course and profile of fever varied between lactating and nonlactating animals, these responses appeared to depend on the physiological state of female animals.

Objective: To determine the Helicobacter pylori infection status in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum. Methods:H. pylori infection was certified by indirect immunofluorescence assay. Aquaporin-4 (AQP4) antibody was detected by cell-based assay. H. pylori seroprevalence was measured in 118 patients with NMO (n = 52), high-risk NMO (hrNMO, longitudinally extensive transverse myelitis, n = 17 and recurrent optic neuritis, n = 7), MS (n = 42) and healthy controls (n = 27). Logistic regression analysis was used to determine associations between H. pylori infection and NMO and MS. Results:H. pylori antibodies were present in 119 serum samples (82.1%, 119/145), with antibody positivity in 90.4% (47/52) of the patients with NMO, 95.8% (23/24) of the patients with hrNMO, 73.8% (31/42) of the patients with MS and 59.3% (16/27) of the controls. NMO spectrum patients had greater positivity for H. pylori than MS patients (p < 0.05) and controls (p < 0.05). The frequency of H. pylori seropositivity did not significantly differ between MS patients and controls (p = 0.726). H. pylori seropositivity was significantly higher in AQP4 antibody-positive patients (54/58, 93.1%; p = 0.038) than in AQP4 antibody-negative patients (48/60, 80%). Logistic regression analysis showed that H. pylori seropositivity was significantly associated with hrNMO [odds ratio (OR) = 9.311, p = 0.005] or hrNMO + NMO (OR = 6.350, p = 0.028). Conclusion:H. pylori infection was present in most Chinese patients with NMO and hrNMO, and may be a risk factor for the NMO spectrum.

Aging in female rats is associated with cessation of reproductive cycles, development of mammary cancer, and increased incidence of autoimmune diseases. Previously, we demonstrated an age-related decline in sympathetic noradrenergic (NA) innervation in the spleen and lymph nodes of female F344 rats accompanied by significantly reduced natural killer cell activity, interleukin (IL)-2 and interferon (IFN)-γ production, and T- and B-cell proliferation, suggesting possible links between sympathetic activity and immunosenescence. Objectives: The aim of this study is to investigate the effects of <smlcap>l</smlcap>-(–)-deprenyl, a monoamine oxidase-B inhibitor, on the sympathetic nervous system and cell-mediated immune responses in old female rats. Methods: Low doses of <smlcap>l</smlcap>-deprenyl (0.25 or 1.0 mg/kg body weight, BW) were administered intraperitoneally to 19- to 21-month-old female F344 rats for 8 weeks. To assess the stereoselectivity of the effects of deprenyl on splenic sympathetic activity and immune responses, the <smlcap>d</smlcap>-enantiomer (<smlcap>d</smlcap>-(+)-deprenyl; 1.0 mg/kg BW) was also included in the studies. Norepinephrine (NE) concentration and content, and mitogen-induced T-cell proliferation and cytokine production were assessed in the splenocytes after deprenyl treatment. Results: Treatment with <smlcap>l</smlcap>-deprenyl reversed the age-related decrease in NE concentration and content and IFN-γ production, and increased IL-2 production in the spleen while <smlcap>d</smlcap>-deprenyl did not affect the age-associated reduction in splenic NE levels or cytokine production. Conclusions: These findings demonstrate that <smlcap>l</smlcap>-deprenyl exerts neurorestorative and immunostimulatory effects on the sympathetic nervous system and cell-mediated immune responses during aging and provides evidence for a causal relationship between some aspects of immunosenescence and the age-related decline in sympathetic nerves in the spleens of female F344 rats.

Background/Aim: Oxytocin (OXT) secretion during cecal ligation puncture (CLP)-induced sepsis has not yet been examined. Although immune properties have been attributed to OXT, its effect on CLP-sensitized macrophages has never been investigated. We analyzed OXT secretion during CLP and its effect in CLP-sensitized macrophage cultures. Methods: Male Wistar rats were decapitated 4, 6 or 24 h after CLP surgery or sham operation and blood, brain and neurohypophyses were collected for OXT measurements. In another set of animals we studied the effect of OXT on nitrite, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-10 production of peritoneal macrophages harvested at 6 and 24 h after CLP. Results: In the early phase of sepsis (4–6 h), OXT levels increased in plasma and decreased in hypothalamus and neurohypophysis. In the late phase (24 h), plasma and neurohypophyseal levels remained basal. In the paraventricular, the OXT content remained low, but in the supraoptic increased. Macrophages of the early phase of sepsis pretreated with OXT and stimulated with lipopolysaccharide showed decreased nitrite, TNF-α and IL-1β levels, but no alteration in IL-10 production. In the late phase, they showed reduction only on IL-1β. Conclusions: OXT secretion during sepsis may represent a neuroendocrine response contributing to the overall host response to infection by decreasing the proinflammatory response and oxidative stress.

Background: Cytokines have been shown to be involved in traumatic brain injury (TBI). We investigated the independent association between serum levels of IL-10 and TNF-α and hospital mortality of patients with severe TBI. Methods: Serum IL-10 and TNF-α levels were determined after a median period (interquartile range (IQ) 25–75) of 10 h (IQ 5–18) after severe TBI in 93 consecutive patients and in randomly selected patients with mild (n = 18) and moderate (n = 16) TBI. In patients with severe TBI, additional blood samples were analyzed 30 h (IQ 22–37) and 68 h (IQ 55–78) after TBI. Age, gender, computed tomography findings, Glasgow Coma Scale score (GCS) and pupil reactions at admission, associated trauma and hospital mortality were collected. Results: Elevated serum levels of IL-10, but not TNF-α, correlated significantly with GCS severity (R2 coefficient, p < 0.0001) and were found to be associated with hospital mortality in patients with severe TBI. Elevated IL-10 remained associated with mortality (p = 0.01) in a subset of patients with isolated severe TBI (n = 74). Multiple logistic regression analysis showed that higher IL-10 levels (>90 pg/ml) at 10 or 30 h after TBI were 6 times (odds ratio (OR) 6.2, 95% confidence interval (CI) 1.2–25.1, p = 0.03) and 5 times (OR 5.4, 95% CI 1.2–25.1, p = 0.03), respectively, more frequently associated with hospital mortality than lower levels (<50 pg/ml), independently of age, GCS as well as pupil reactions at admission and associated trauma. Conclusions: Serum IL-10 levels may be a useful marker for severe TBI prognosis.