Attenuation of the levels of pro-inflammatory cytokines prevents depressive-like behavior during ethanol withdrawal in mice.

Clinical studies indicate that alcohol-dependent patients may develop depressive symptoms during abstinence, which may increase the likelihood of relapse. It is known that both in alcohol exposure and depression, there is an increase in the levels of pro-inflammatory cytokines in the brain. However, the putative contribution of increased levels of pro-inflammatory cytokines in the development of depressive-like behavior during ethanol withdrawal has not been evaluated. In the present study, we aimed to investigate if ethanol withdrawal-induced depressive-like behavior is related to increased levels of pro-inflammatory cytokines in the brain. Male mice were treated with vehicle (saline 0.9%, v.o.) or ethanol (2 g/kg, v.o.) for 14 days. After 5 days of cessation of the ethanol treatment, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT) and then sacrificed. Their brains were analyzed for the levels of pro-inflammatory cytokines. Ethanol withdrawal mice showed increased immobility time in the FST and TST than by the control group, indicating increased depressive-like behavior. No alterations in OFT were observed. Ethanol withdrawal increased the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus and striatum, interleukin-1 beta (IL-1ß) in the hippocampus, and IL-6 in the prefrontal cortex and hippocampus. Treatment of mice with nimesulide (5 or 10 mg/kg/day), a cyclooxygenase-2 inhibitor, during ethanol withdrawal prevented the increase in immobility time in the TST. Similar results were observed in the FST upon nimesulide treatment, although with a higher dose. Nimesulide treatment (10 mg/kg) prevented the ethanol withdrawal-induced alterations in the levels of TNF-α, IL-1ß, and IL-6 in the hippocampus, prefrontal cortex, and striatum. Treatment of mice with an atypical antidepressant drug, vilazodone (0.3 or 1 mg/kg) prevented the increase in depressive-like behavior induced by ethanol withdrawal in the TST. In the FST, the increase in immobility time was prevented only by 1 mg/kg vilazodone treatment. Vilazodone prevented the increase in the levels of TNF-α, IL-1ß, and IL-6 in the hippocampus, IL-6 in the prefrontal cortex, and TNF-α in the striatum. In conclusion, these data indicate that increased levels of pro-inflammatory cytokines may play a role in the development of depressive-like behavior during ethanol withdrawal in mice.

Atorvastatin prevents lipopolysaccharide-induced depressive-like behaviour in mice.

Clinical and pre-clinical evidences indicate an association between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Atorvastatin is a cholesterol-lowering statin that possesses pleiotropic effects including neuroprotective and antidepressant actions. However, the putative neuroprotective effect of atorvastatin treatment in the acute inflammation mice model of depressive-like behaviour has not been investigated. In the present study, we aimed to investigate the effect of atorvastatin treatment on lipopolysaccharide (LPS) induced depressive-like behaviour in mice. Mice were treated with atorvastatin (1 or 10 mg/kg, v.o.) or fluoxetine (30 mg/kg, positive control, v.o.) for 7 days before LPS (0.5 mg/kg, i.p.) injection. Twenty four hours after LPS infusion, mice were submitted to the forced swim test, tail suspension test or open field test. After the behavioural tests, mice were sacrificed and the levels of tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), glutathione and malondialdehyde were measured. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment prevented LPS-induced increase in the immobility time in the forced swim and tail suspension tests with no alterations in the locomotor activity evaluated in the open field test. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment also prevented LPS-induced increase in TNF-α and reduction of BDNF levels in the hippocampus and prefrontal cortex. Treatment with atorvastatin (1 or 10 mg/kg/day) or fluoxetine prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus and prefrontal cortex. The present study suggests that atorvastatin treatment exerted neuroprotective effects against LPS-induced depressive-like behaviour which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.

Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice.

Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a hormone synthesized and secreted by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like effects. In this way, it would be interesting to evaluate the putative antidepressant-like effect of melatonin treatment in an acute inflammation mice model of depression. The present study aimed to investigate the effect of melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior, neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic fator (BDNF) levels. Mice were treated with melatonin (10 mg/kg, i.p.) 30 min before LPS (0.5 mg/kg, i.p.) injection. Twenty-four hours after LPS infusion, mice were submitted to the behavioral tests and, thereafter, biochemical determinations were performed. Melatonin treatment prevented LPS-induced depressive-like behavior in the forced swim and tail suspension tests with no alterations in locomotor activity evaluated in the open field test. Melatonin attenuated LPS-induced increase in tumor necrosis factor-α (TNF-α) and reduction of BDNF levels in the hippocampus. Treatment with melatonin also prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus. In conclusion, the present study suggests that melatonin treatment exerted neuroprotective effects against LPS-induced depressive-like behavior which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.

Mycophenolate mofetil has potent anti-inflammatory actions in a mouse model of acute lung injury.

Septic shock is a systemic inflammatory response syndrome, and it is the leading cause of death in intensive care units. Mycophenolate mofetil (MMF) is an immunosuppressant that has been shown to be effective in the treatment of various inflammatory diseases. In this study, the anti-inflammatory effect of MMF in a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS) was evaluated. ALI was induced by intrapleural injection of LPS (250 ng/cavity). The leukocyte migration, exudation, myeloperoxidase and adenosine deaminase activities, nitric oxide products, tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1ß) levels, as well as mRNA expression of TNF-α and IL-1ß, were evaluated. This study showed that MMF significantly decreased all parameters studied in a manner comparable to treatment with dexamethasone. In conclusion, MMF has important anti-inflammatory effects that may be useful as an auxiliary treatment for septic shock.

Screening for latex sensitization by questionnaire: diagnostic performance in health care workers.

BACKGROUND: Latex allergy has emerged as a major cause of allergic reactions in health care workers. However, information is limited regarding the diagnostic methods available. OBJECTIVE: The aim of this study was to investigate diagnostic performance (sensitivity, specificity, and predictive values) of screening for natural rubber latex sensitization by questionnaire among health care workers, using skin prick test (SPT) as the gold standard for diagnosis. METHODS: The study population consisted of 260 randomly selected health care workers from the public health units in the city of Florianopolis, Brazil. The subjects were recruited from 2 groups: those who used latex gloves in their work (140) and those who were not exposed to latex (120). The mean (SD) age of the study population was 38.6 (0.6) years. Logistic regression analysis was used to predict SPT result from the questionnaire on previous symptoms of latex sensitization. RESULTS: Symptoms of (1) dryness, fissuring, swelling, pruritus, or cutaneous rash on the hands, and (2) pruritus of the oral mucosa or local redness after eating certain fruits (avocados, bananas, kiwis, chestnuts, mango, melons, or peaches) were the most sensitive and specific questionnaire items, respectively. The combination of these items with a cutoff point derived from the logistic regression led to 100% sensitivity and specificity for the prediction of SPT results in the population studied, with 95% confidence intervals of 51.7% to 100% for sensitivity and 98.1% to 100% for specificity. CONCLUSION: A questionnaire applied in a group of health care workers displayed excellent screening performance for latex sensitization.

Latex allergen sensitization and risk factors due to glove use by health care workers at public health units in Florianopolis, Brazil.

BACKGROUND: Natural rubber latex allergy is a "new" illness whose prevalence has reached epidemic proportions in highly exposed populations such as health care professionals. OBJECTIVE: The aim of the study was to evaluate the frequency of reactions to latex and risk factors due to glove use in health care workers (HCW) in Florianopolis, Santa Catarina, Brazil. METHODS: We evaluated latex-related allergy in 260 HCW by means of a questionnaire, skin prick tests (SPT) and serum latex specific IgE antibody levels. The subjects were divided into two groups depending on level of exposure to latex gloves. Comparisons were made between the different variables and a risk score was calculated using logistic regression analysis. RESULTS: Glove-related symptoms were observed in 57% of 140 HCW. Significant differences between HCW and control groups were found for the following symptoms: contact dermatitis (P < .0001), cutaneous rash (P < .0001), asthma or allergic rhinitis (P < .0001), symptoms associated with toy balloons (P < .0001), airborne glove powder causing latex allergen reaction (P < .0001), food allergy (P < .0001), fruit allergy (P < .0001) and multiple surgical interventions (P = .0052). Contact dermatitis and anaphylaxis were the main problems, with a high risk factor for the development of latex allergy. Logistic regression analysis showed a significant positive association between the risk of latex allergy and those subjects who reported more than 4 positive answers on the questionnaire (including SPT) (odds ratio 6.8; 95% confidence interval 0.7-60.3). No latex-related allergy symptoms were reported by the control group. Serological latex specific immunoglobulin (Ig) E antibody levels were negative for both groups. CONCLUSION: It is essential to recognize which professionals are sensitized to latex in order to provide appropriate treatment and to establish adequate prevention.