Evidence for an immune response in major depression: A review and hypothesis
ABSTRACT 1.1. This paper reviews recent findings on cellular and humoral immunity and inflammatory markers in depression.2.2. It is shown that major depression may be accompanied by systemic immune activation or an inflammatory response with involvement of phagocytic (monocytes, neutrophils) cells, T cell activation, B cell proliferation, an “acute” phase response with increased plasma levels of positive and decreased levels of negative acute phase proteins, higher autoantibody (antinuclear, antiphospholipid) titers, increased prostaglandin secretion, disorders in exopeptidase enzymes, such as dipeptidyl peptidase IV, and increased production of interleukin (IL)-1β and IL-6 by peripheral blood mononuclear cells.3.3. It is hypothesized that increased monocytic production of interleukins (Il-1β and Il-6) in severe depression may constitute key phenomena underlying the various aspects of the immune and “acute” phase response, while contributing to hypothalamic-pituitary-adrenalaxis hyperactivity, disorders in serotonin metabolism, and to the vegetative symptoms (i.e. the sickness behavior) of severe depression.
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ABSTRACT: Numerous studies have demonstrated that inflammation, oxidative stress and altered level of neurotrophins are involved in the pathogenesis of depressive illness. Mangiferin, a C-glucosylxanthone is abundant in the stem and bark of Mangifera indica L. The compound has been shown to possess antioxidant, anti-inflammatory and immunomodulatory activities. The present study was performed to investigate the effect of mangiferin pretreatment on lipopolysaccharide-induced increased proinflammatory cytokines, oxidative stress and neurobehavioural abnormalities. Mice were challenged with lipopolysaccharide (0.83mg/kg, i.p.) after 14 days of mangiferin (20 and 40mg/kg, p.o.) pretreatment. Mangiferin pretreatment significantly ameliorated the anxiety-like behavior as evident from the results of an elevated plus maze, light-dark box and open field test. Mangiferin pretreatment also improved the anhedonic behaviour as revealed by sucrose preference test and increased social interaction time. It also prevented the lipopolysaccharide-evoked depressive-like effect by reducing the immobility time in forced swim and tail suspension test. Lipopolysaccharide-induced elevated oxidative stress was decreased with mangiferin pretreatment due to its potential to increase reduced glutathione concentration, superoxide dismutase and catalase activity and decrease lipid peroxidation and nitrite level in the hippocampus as well as in the prefrontal cortex. Mangiferin pretreatment also attenuated neuroinflammation by reducing the interleukin-1 beta (IL-1β) level in hippocampus and prefrontal cortex. In conclusion, our results demonstrated that mangiferin possessed antidepressant and anti-anxiety properties due to its ability to attenuate IL-1β level and oxidative stress evoked by intraperitoneal administration of lipopolysaccharide. Mangiferin may be a potential therapeutic agent for the treatment of depressive and anxiety illness.European Journal of Pharmacology 07/2014; 740:337–345. · 2.68 Impact Factor
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ABSTRACT: Based on the urgent need for reliable biomarkers in relation to suicide risk both for more accurate prediction as well as for new therapeutic opportunities, several researchers have been studied evidences of the potential participation of inflammatory processes in the brain, in particular cytokines, in suicide. The purpose of this review was to analyze the associations between inflammation markers and suicide.Methods To achieve this goal, a systematic review of literature was conducted via electronic database Scopus using the Medical Subject Headings (MeSH) terms: “cytokines”, “suicide” and “inflammation”. Through this search it was found 54 articles. After analyzing them 15 met the eligibility criteria and were included in the final sample.ResultsOne of the most mentioned inflammatory markers was Interferon-α (IFN-α), a pro-inflammatory cytokine which has been shown to increase serum concentrations of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-a (TNF- α) and IFN-ϒ, which are factors increased suicide victims and attempters. In this line, IL-6 is not only found to be elevated in the cerebrospinal fluid of suicide attempters, even its levels in the peripheral blood have been proposed as a biological suicide marker. Another study stated that increased levels of IL-4 and IL-13 transcription in the orbitofrontal cortex of suicides suggest that these cytokines may affect neurobehavioral processes relevant to suicide.LimitationsA lack of studies and great amount of cross-sectional studies.Conclusion Inflammation may play an important role in the pathophysiology of suicide, especially, levels of some specific inflammatory cytokines.Journal of Affective Disorders 10/2014; · 3.71 Impact Factor
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ABSTRACT: We recently discovered that the antidepressant sertraline is an effective inhibitor of hippocampus presynaptic Na+ channel permeability in vitro and of tonic-clonic seizures in animals in vivo. Several studies indicate that the pro-inflammatory cytokines in the central nervous system are increased in epilepsy and depression. On the other hand inhibition of Na+ channels has been shown to decrease pro-inflammatory cytokines in microglia. Therefore, the possibility that sertraline could overcome the rise in pro-inflammatory cytokine expression induced by seizures has been investigated. For this purpose, IL-1β and TNF-α mRNA expression was determined by RT-PCR in the hippocampus of rats administered once, or for seven consecutive days with sertraline at a low dose (0.75 mg/kg). The effect of sertraline at doses within the range of 0.75 to 25 mg/kg on the increase in IL-1β and TNF-α mRNA expression accompanying generalized tonic-clonic seizures, and increase in the pro-inflammatory cytokines expression induced by lipopolysaccharide was also investigated. We found that under basal conditions, a single 0.75 mg/kg sertraline dose decreased IL-1β mRNA expression, and also TNF-α expression after repeated doses. The increase in IL-1β and TNF-α expression induced by the convulsive agents and by the inoculation of lipopolysaccharide in the hippocampus was markedly reduced by sertraline also. Present results indicate that a reduction of brain inflammatory processes may contribute to the anti-seizure sertraline action, and that sertraline can be safely and successfully used at low doses to treat depression in epileptic patients.PLoS ONE 11/2014; 9(11):e111665. · 3.53 Impact Factor