Changes in cytokine levels in major depression and during treatment have been reported in adults. However, few studies have examined cytokine levels in an adolescent sample despite this being a common age of onset. Methods. We measured proinflammatory (IL-2, IFN-γ, IL-1β, TNF-α, IL-6, IL-12, and IL-15) and anti-inflammatory (IL-4, IL-5, IL-13, IL-1Ra, and IL-10) cytokine serum levels in 22 adolescents with major depression and 18 healthy volunteers. Cytokines were measured by multiplex bead-based immunoassays at baseline, and 4 and 8 weeks after commencement of fluoxetine administration in the clinical group. Results. Compared to healthy volunteers, adolescents with major depression at baseline showed significant increases in all pro- and anti-inflammatory cytokines, except IL-1Ra and IL-10. Significant changes were observed in fluoxetine treatment compared to baseline: proinflammatory cytokines IFN-γ, IL-1β, TNF-α, IL-6, IL-12, and IL-15 were decreased only at week 4 whereas IL-2 was increased only at week 8; anti-inflammatory cytokines IL-4 and IL-5 were increased at week 8 while IL-1Ra was reduced only at week 4. There were no significant correlations between cytokine levels and symptomatic improvement in HDRS. Discussion. The results suggest a significant interplay between cytokine levels, the depressive state, and the stage of treatment with an SSRI. To the best of our knowledge, this is the first report in depressed adolescents with elevated IL-12, IL-13, and IL-15 levels. Further studies are necessary to clarify the role and mechanisms of altered cytokine levels in the pathogenesis and physiopathology of major depressive disorder.

Parturition in mammals demands a precise coordination of several neuro-immune-endocrine interactions including: a sterile inflammatory response that involves secretion of inflammation mediators like cytokines/chemokines; changes in the secretion of hormones such as progestogen, estrogens, cortisol, and oxytocin; as well as adjustments of the neuroautonomic function. Specifically, the so-called cholinergic anti-inflammatory pathway seems to play a key role in the homeostasis of the neuro-immune-endocrine axis by adjusting the vagus nerve activity during parturition. Here, we provide insights into the importance of the vagus during parturition from an autonomic, endocrine, and immune interplay perspective, and describe the potential role of heart rate variability analysis to explore these interactions noninvasively, economically, and accessibly.

Murine leprosy, caused by Mycobacterium lepraemurium (MLM), is a chronic disease that closely resembles human leprosy. Even though this disease does not directly involve the nervous system, we investigated a possible effect on working memory during this chronic infection in Balb/c mice. We evaluated alterations in the dorsal region of the hippocampus and measured peripheral levels of cytokines at 40, 80, and 120 days post-infection. To evaluate working memory, we used the T-maze while a morphometric analysis was conducted in the hippocampus regions CA1, CA2, CA3, and dentate gyrus (DG) to measure morphological changes. In addition, a neurochemical analysis was performed by HPLC. Our results show that, at 40 days post-infection, there was an increase in the bacillary load in the liver and spleen associated to increased levels of IL-4, working memory deterioration, and changes in hippocampal morphology, including degeneration in the four subregions analyzed. Also, we found a decrease in neurotransmitter levels at the same time of infection. Although MLM does not directly infect the nervous system, these findings suggest a possible functional link between the immune system and the central nervous system.

BackgroundResident alveolar macrophages, dendritic cells, and immigrating neutrophils (NEU) are the first cells to contact Mycobacterium tuberculosis in the lung. These cells, and additional lymphoid cells in the developing granuloma, release a series of components that may concentrate in the serum and affect disease progression.PurposeThe aim of this study was to investigate the effect of the serum from tuberculosis (TB) patients and their household contacts (HHC) on the nuclear morphology of NEU.Materials and methodsNEU from healthy (HLT) people were incubated with sera from patients with active pulmonary TB, their HHC, and unrelated people. Changes in the nuclear morphology of NEU were analyzed by light and electron microscopy.ResultsSera from patients with TB induced changes in the nuclear morphology of NEU that included pyknosis, swelling, apoptosis, and netosis in some cases. Sera from some HHC induced similar changes, while sera from HLT people had no significant effects. Bacteria did not appear to participate in this phenomenon because bacteremia is not a recognized feature of nonmiliary TB, and because sera from patients that induced nuclear changes maintained their effect after filtration through 0.22 µm membranes. Neither anti-mycobacterial antibodies, TNFα, IL-6, IFNγ, or IL-8 participated in the phenomenon. In contrast, soluble mycobacterial antigens were likely candidates, as small quantities of soluble M. tuberculosis antigens added to the sera of HLT people led to the induction of nuclear changes in NEU in a dose-dependent manner.ConclusionThese results might help to detect subclinical TB within HHC, thus leading to a recommendation of prophylactic treatment.

Aim of the Study: The primary aim of the study was to test the effect of 2,4,5-trimethoxy-1-propenylbenzene (alpha asarone), a hypocholesterolaemic drug, on the progression of collageninduced arthritis (CIA) in mice. Olive oil, the vehicle of alpha-asarone, and dexamethasone were used as control treatments. Set-Up: Four groups of DBA/1 mice were immunised with chicken type II collagen (CII) via the intradermal route and either left untreated or were treated with alpha asarone, olive oil, or dexamethasone. A non-immunised group was an additional control. Follow-Up: The thicknesses of the rear and front footpads were continuously monitored, and the levels of anti-collagen antibodies were measured at the end of the experiment. The animals were then sacrificed, and their rear and front limbs were removed and processed for histological examination. Results: Alpha asarone had no anti-inflammatory effect on CIA, and in one-third of the animals, it showed a pro-inflammatory effect that was characterised by a marked accumulation of neutrophils. Olive oil did not show any obvious anti-inflammatory effect on CIA, but it lowered the level of CII anti-bodies by 50%, suggesting a potential long-term anti-inflammatory effect. As expected, dexamethasone had a clear anti-inflammatory effect on CIA. Conclusion: Alpha asarone did not show any antiinflammatory effect on CIA in the mice under the above conditions; however, the accumulation of neutrophils in the CIA lesions of mice treated with alpha asarone and the effect of olive oil in downregulating the levels of anti-CII antibodies in CIA are two findings that warrant further investigation.