Biotechnologically obtained bacterial melanin (BM) has been extensively studied as a potential pharmacological preparation with neuroprotective and anti-inflammatory effects. Anti-inflammatory action of BM was tested in animal model of induced encephalomyelitis. The goal of presented research was to examine anti-inflammatory potential of BM in lipopolysaccharide-stimulated murine RAW 264.7 cells. The cells were treated with different concentrations of BM (from 6 mg/ml to 4, 2 and 1 mg/ml) and incubated for 20 hours. Results were compared with data obtained from vehicle control treated cells. Two tailed t-test was used to evaluate the results. The obtained data showed that BM reduces the production of nitric oxide and prostaglandin E2. The substance suppresses production of pro-inflammatory cytokines including interleukin (IL)-6 and IL-1b. The results revealed that BM has anti-inflammatory activity and has a potential to suppress neuroinflammation. Brain macrophages-are the only cells that mediate brain inflammation. Extracellular neuromelanin can activate the CNS microglia inducing neuroinflammation and neurodegeneration. The water-soluble biotechnological melanin does not activate microglia - the resident brain macrophages.
Today the term "stress" is used for diverse conditions, which causes confusion. We propose to use the term stress for beneficial stimuli, in which the genome is altered in healthy animals, and men, and thus protected from environmental and other stressful conditions. The mutations induced are inheritable. The innate immune system initiates the distress reactions, which are analogous to the acute phase responses. Injury, infections, noxious agents, emotional disturbances may cause distress. Innate immunity responds to injury, infectious disease, noxious agents, and environmental impulses. Emotional distress is first perceived by the central nerves system and then innate immunity is activated by glucocorticoids and catecholamines. The innate immune system provides natural antibodies, killer thymus derived lymphocytes and suppressor-regulatory thymus derived cells, which are activated. A recently discovered neuroprotective thymus derived lymphocyte is also generated. Fever and catabolism prevail, which is a sickness behavior. Innate immune cells recognize germ line derived mayor histocompatibility antigens as "self" and protect it. If germ line mayor histocompatibility genes mutate, the innate immune antigen receptors will also change and now this "altered self" will be regarded as "self" and will be protected by innate immunity.
The relationship between exercise and the immune system (IS) is a subject that has had widespread attention across time. Both types of behavior, lack of exercise/exhausting exercise, are suggested to weaken immunity. On the contrary, regular moderate exercise seems to boost it. The effects of exercise over the immune responses must be well determined in order to understand how lack of exercise increases the susceptibility to viral, bacterial, and parasitic infections. Nonetheless, we must keep in mind that the relation between physical activity and health is not as direct as it seems, for instance, greater susceptibility to infections after strenuous exercise bouts has been reported, and no impact at all over the immune system is reported during and after low-intensity bouts. Some of the parameters from the immune system that are affected when exercise is performed to exhaustion are: levels of salivary IgA, impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, up-regulation of CD14+ cells, variations in CD4+ and CD8+ T lymphocytes proportion, among others. This review discusses the evidence of the effects that exercise elicits on the immune response on different conditions, presenting an updated view about it. Furthermore, we will underline the evidence about the different effects provoked by exercise when performed at distinct intensities and durations. Finally, we will focus on the molecular mechanisms that offer substrate to these interactions and how they help us understand it.
The circadian oscillator system is known to affect various immune functions. These actions can be attributed to either direct effects of oscillator components, including those present in peripheral cellular clocks, or to indirect actions via strongly rhythmic regulators such as melatonin and glucocorticoids. The aim of this article is to outline the connections between circadian and immune systems at the level of regulation by noncoding RNAs. Numerous pleiotropically acting miRNAs are summarized that display functions in both systems. Many miRNAs that regulate inflammation are shown to harbor putative or demonstrated binding sites for oscillator components in their respective promoters or to be under control of melatonin or glucocorticoids. Melatonin, which possesses immune modulatory properties, has been shown to act partially via upregulation of sirtuin-1, a regulator that participates in inflammation control and also increases circadian amplitudes. Thus, both melatonin and sirtuin-1 can be regarded as connecting factors between circadian and immune systems. Additional bridging effects can be expected from other noncoding RNAs, in particular, circRNAs and rhythmically expressed lncRNAs. Various circRNAs are listed that sponge miRNAs under circadian control. Moreover, the intercellular spreading of information transmitted by miRNAs, circRNAs and lncRNAs via exosomes and ectosomes is addressed.
Autism Spectrum Disorder (ASD) includes a group of neurodevelopmental disorders associated with the dysregulation of cytokine profile. The family of suppressors of cytokine signaling (SOCS) has been demonstrated to exert negative regulation on production of cytokines via interference with the Jak/Stat transduction pathway. In the present study, we evaluated expression of SOCS1-3 and SOCS5 in the peripheral blood of ASD patients compared to the healthy subjects by means of real time PCR. Expression levels of SOCS genes were not significantly different between cases and controls. Significant correlations were found between expression levels of SOCS genes in female subjects, but not in male subjects. In addition, based on the Spearman correlation coefficients, correlations were more significant in ASD patients compared to the healthy subjects. SOCS3 expression levels were significantly correlated with the age of all studied participants. SOCS5 expression was correlated with the age of patients, but not healthy subjects. Although we demonstrated similar levels of SOCS genes expression in peripheral blood of ASD patients and healthy subjects, based on the observed altered cytokine profile of ASD patients, we suggest future evaluation of expression of these genes in certain components of blood.
Interleukin 6 (IL-6) is a typical pleiotropic cytokine that modulates a variety of physiological events in vertebrates, including cell proliferation, differentiation, survival, and apoptosis, among other functions. IL-6 plays roles in the immune, the endocrine, the nervous, and the hematopoietic systems, in bone metabolism, regulation of blood pressure and inflammation. IL-6 exerts its effects on different tissues and organ systems. Many cell types are reported to produce IL-6: T cells, B cells, polymorphonuclear cells, eosinophils, monocyte/macrophages, mast cells, dendritic cells, chondrocytes, osteoblasts, endothelial cells, skeletal and smooth muscle cells, islet cells, thyroid cells, fibroblasts, mesangial cells, keratinocytes, microglial cells, astrocytes, oligodendrocytes, adipose tissue and certain tumor cells. In this article we review the participation of the IL-6 in the neuroimmunoendocrine network that includes all interactions across species, sexes, cells, and types of responses. Additionally, we discuss the information that is available so far about the production of IL-6 by the neural cell populations, the role that this cytokine plays at the local level in the modulation of some physiological neural actions, as well as its participation in the development and progression of neuroinflammation and the neurodegenerative process. Considering the multiple functions that IL-6 plays as an endocrine and neural regulator, the specific targeting of the IL-6 pathway can be a promising new approach for the treatment and prevention of neurodegenerative disorders in humans. Furthermore, blocking the effect of IL-6 may improve the autoinflammatory process both systemically and locally.
Breast cancer (BC) is one of the oncological diseases most frequently diagnosed in adult women worldwide. As with other cancer types, BC is thought to emerge after genetically susceptible stem epithelial cells display uncontrolled proliferation after being chronically exposed to stressful environmental conditions that may include altered hormonal profiles, metabolic status and/or surrounding environmental settings. This scenario, nonetheless, fails to recognize the role that psychological factors play on BC origin, progression and outcome. Accordingly, in the preceding work, we present data that supports that some psychological traits may predispose Mexican women to develop BC. In this complementary paper, we now explore the "relative weight" that emotional suppression and repression and stress symptoms have on the likelihood of women developing BC by establishing, through network analyses, the way these psychological traits interact with well accepted BC-risk environmental, genetic and physiological factors. Since in our model nodes represent personality traits and the links among them (i.e. the "activated" psychic pathways), Pearson's correlation analyses were used to evaluate whether healthy networks are different among health-disease states. In addition, in order to study the associations with the clinical factors, an analysis of principal components (PC) and three multivariate models were constructed in order to determine with precision the psychological predictors of BC. Results show that the psychological traits, as expected, adopt a network organization, in which BC patients had the most disconnected distribution, followed by the Benign Breast Pathology (BBP) group. Breast pathology according to the resulting network seems to disconnect emotions from the stress response. Our results also show that the variance found between groups can only be explained by psychological traits, that is, in this sample only certain psychological traits increase the susceptibility to BC but none of the most recognized clinical factors do.
The neuroendocrine-immune network is composed by the immune, nervous and endocrine systems; it regulates a number of different physiological processes such as fertility, gestation, immune response, and behavior, among others. An unbalanced network could result in the compromised function of the previously mentioned physiological processes besides potentially inducing inflammatory diseases or depressive behavior. Cadmium (Cd) is a toxic metal whose effects extend over the network's components affecting the function of the hypothalamus, hypophysis, suprarenal glands and gonads, as well as of immune cells and the organism in general. Cd toxicity is mostly due to oxidative stress; however, this metal is also a known endocrine disruptor interfering with hormone synthesis and signaling in addition to several metabolic processes. In the present manuscript we review the direct effect of Cd toxicity on various components of the neuroendocrine-immune network as well as some of its derived pathological consequences.
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of human central nervous system (CNS). OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family. Ligation of OX40 is crucial for clonal expansion of antigen-specific T-cells as well as survival and generation of T-cell memory. Soluble OX40 is the soluble form of OX40 and it has been demonstrated that it is correlated with some autoimmune disorders. OBJECTIVES: The purpose of this study was to investigate serum levels and gene expression of OX40 as a paraclinical marker in MS patients compared to the healthy control group. METHODS: In this research, 40 new cases of MS patients and 40 healthy people as control group were investigated. After extracting RNA from peripheral blood and cDNA synthesis, we examined gene expression using real-time PCR technique, and serum level of soluble OX40 was measured by commercially available ELISA kit. Additionally, Mann-Whitney test was used to compare the gene expression and serum levels between two groups. RESULTS: We did not find any significant correlation between OX40 gene expression and MS disease (p = 0.715). Soluble OX40 serum levels of MS patients were not significantly different from the control group (P = 0.409). CONCLUSIONS: According to the results of the current study, expression of OX40 gene as an inflammatory factor in peripheral blood and also serum levels of OX40 could not be considered paraclinical markers of this disease.
OBJECTIVE: The aim of this study was to explore the associations between immunological markers and anthropometric measures with linear/nonlinear parameters corresponding to the superficial electromyographic activity of uterus, or electrohysterogram (EHG), at parturition. METHODS: Ten minutes of EHG signals were recorded from twenty healthy volunteers in active labor at term (40 +/- 1 weeks). These signals were normalized and analyzed to estimate relevant linear and nonlinear parameters such as the average root mean square (RMS) value, the area under the curve (AUC) and the sample entropy (SampEn). Furthermore, serum levels of several maternal molecules associated with the inflammatory response in active labor such as the interleukin (IL)-10 family, the B cell activating factor belonging to the TNF family (BAFF/TNFSF13B), and the soluble hemoglobin scavenger receptor CD163 (sCD163) were all analyzed using multiplex immunoassays. In addition, we obtained maternal anthropometric measures such as the body mass index (BMI), weight, abdominal and hip circumference. RESULTS: We found several moderate but significant positive correlations between the SampEn of the EHG signals with BMI: r = 0.54, p = 0.01; weight: r = 0.41, p = 0.03 and hip circumference: r = 0.38, p = 0.04. Also, the average RMS of EHG signals exhibited moderate positive significant correlations with IL-28A: r = 0.48, p = 0.01; sCD163: r = 0.43, p = 0.02 and BAFF/TNFSF13B: r = 0.49, p = 0.01. CONCLUSION: Our results show that larger anthropometric measures were associated with higher irregularity of uterine electrical activity, and that elevated serum concentrations of IL-28A, BAFF/TNFSF13B and sCD163 were related to increased uterine muscle activity. These findings suggest an interaction among anthropometric measures, uterine activity, and inflammatory parameters at active labor.
Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), mainly in dependency upon a complex interplay between lymphocytes and innate cells. As such, the role for hematopoietic cells, their extravasation into the CNS and their mechanisms for neurodegeneration have been extensively studied and discussed elsewhere. On the other hand, neurons, oligodendrocytes, astrocytes and microglia also produce mediators that contribute to the local microenvironment and either regulate or potentiate neurodegeneration, but their contribution to the whole phenomenon has been largely neglected. In this review we will address the crosstalk between neurons, glial cells and the immune system, discussing the neuroimmune interactions that may serve as important targets for future drug development.
The protein inhibitor of activated STAT (PIAS) protein family participates in regulation of pathways triggered by cytokines. On the other hand, recent data point to the role of immune dysregulation in the pathogenesis of autism spectrum disorder (ASD). In the present study, we evaluated expression of PIAS genes in peripheral blood of 30 Iranian ASD patients and 41 age-and gender-matched normal subjects by means of quantitative real time PCR. PIASx expression was significantly correlated with age in ASD patients but not healthy subjects. No significant difference was found in expression of PIAS genes between cases and controls. Spearman correlation analysis showed significant correlations between PIAS transcript levels in nearly all study subgroups. However, PIAS1 transcript levels were not correlated with those of PIAS3 and PIASy in male subjects. Moreover, PIAS1 expression was not correlated with expression of PIASx and PIASy in ASD patients in spite of significant correlation in healthy subjects. The results of current study indicate a context-dependent interactive network between PIAS genes and warrant future studies to elaborate the role of these genes in ASD.
Breast cancer (BC) is one of the leading causes of death among women worldwide. Identification of susceptible women might help us reduce BC-related deaths. Traditionally women's susceptibility to BC has been estimated based on family, reproductive and nutritional histories and/or genotyping. Unfortunately, predictions made based on all these factors remain imprecise. Research conducted over the past decades supports the premise that patients displaying some personality traits are prone to develop cancer. Nevertheless, conflicting results have been published. We then conducted a study aimed at evaluating relationships between specific personality traits and different types of breast pathology. This approach aimed at evaluating whether personality profiling, in conjunction with other parameters might help us, in the near future, to identify more accurately Mexican women susceptible to develop BC. As a first step towards this goal, we asked whether healthy women and patients having signs of benign breast pathology or cancer shared or not specific personality traits. We used the Courtauld Emotional Control Total Score, the Weinberger Adjustment Inventory and the Symptoms of Stress Inventory to identify personality traits. Our results indicated that women diagnosed with benign or malign breast pathology share low restraint, low global stress symptoms, low physical stress symptoms, low restraint-defensiveness composite and high distress before diagnosis. This outcome was independent of the educational level, as well as of family, reproductive and nutritional histories, supporting that the weight of the psychological traits is greater than that of the latter variables, at least in our sample.
In this paper the development and current status of Neuroimmune Biology (NIB) is summarised and the extended NISS is discussed. The significance of this newly emerging science is the demonstration that NISS coordinates host defence against infection and other pathogenic agents. Indeed NISS is in control of the biology of higher organisms for their life time.
The immunoneuroendocrine network interactions between prolactin (PRL) and the immune system are important because PRL modulates humoral and cellular immune responses in both physiological and pathological situations, as it occurs in parasitic diseases. Protozoa parasites such as Leishmania sp, Toxopasma gondii, Trypanosoma cruzi or Plasmodium falciparum induce inflammation and raise the release of pro-inflammatory cytokines. PRL triggers anti-parasitic activities, in cells of the immune system at multiple levels, either increasing NK cytolytic activities or enhancing phagocytosis and T helper cytokines 1 (Th1) immune responses. On the contrary, PRL also may promote infections caused by helminthic parasites such as Toxocara canis, or Taenia solium, these parasites possess PRL receptors and could use PRL to increase their growth, movement or reproduction.
Multiple Sclerosis (MS) is an autoimmune-mediated disorder that affects the Central Nervous System (CNS). It is associated with several genetic and environmental risk factors and has a heterogeneous nature that affects the evolution of the disease, as well as its clinical manifestations, which rend ers difficult the follow-up of the patients with MS and their treatment. As in other autoimmune diseases, sex hormones play an important role in the evolution of MS. The prevalence of MS is in a proportion of 2-to-3 females per males, with females more affected and with pregnancy providing a protection state. Sex hormones modulate the immune response and have neuroprotective effects; therefore, treatment with these hormones may ameliorate the clinical status of MS. Because it remains unclear whether sex hormones could modify the response to immunomodulatory treatment by inducing a gender-dependent effect, and whether there are gender-associated biomarkers, which that allow a more detailed and predictive follow-up in patients with MS. Here we review the existing evidence about the search for biomarkers for the clinical follow-up of patients with MS, considering gender as a factor that influences the progression of the disease and the response to treatment. We analyze and discuss the microarray approach, polymorphisms (such as Single Nucleotide Polymorphisms, SNP) and soluble biomarker determinations, which revealed differences depending on the gender of the patients. We propose that further studies must always consider the gender of the patients as a variable in their analysis, which permits a better understanding of the pathogenesis of the disease and obtaining a much better and consistent profile of the biomarkers useful in the clinic of the MS.
Traditionally, prolactin has been the only hormone associated with the reactivation of arrested Toxocara canis larvae in pregnant bitches. Nevertheless, recent findings have shown the effect of progesterone on the host immune response and on the physiology and behavior of the parasite, which probably causes the reactivation of arrested larvae in pregnant bitches. The initial presence of T. canis larvae in the organs of the host causes a non-specific inflammatory infiltrate to surround the larvae, after which a Th1-type response is induced, which is characterized by the recruitment of macrophages and leukocytes, and the production of Interferon-gamma (IFN gamma) and pro-inflammatory cytokines that participate in granuloma formation. In parallel, a Th2-type response is mounted, which regulates the severity of the granulomatous infiltrate that surrounds the larvae, helps in larvae survival and likely favors larval arrest. Larvae in pregnant bitches are reactivated in the second part of gestation, which is characterized by an initial increase in progesterone followed by an increase in prolactin. Progesterone modulates the immune response and induces an increase in anti-inflammatory cytokines, especially interleukin (IL)10, which decreases the severity of the granulomatous response, creating favorable conditions for larval arrest. Furthermore, progesterone and prolactin stimulate the growth and development of larvae in vitro through action on possible receptors for these hormones. In conclusion, there is wide evidence of a strong association between both hormones and T. canis larvae reactivation in the second part of gestation in bitches.
The immune system plays an essential role in distinguishing between self and non-self and hence protecting the host from infections. Upon the pathogen encounter, the host seeks to ensure an adequate inflammatory reaction to combat infection but at the same time tries to prevent collateral damage due to excessive immune activation. As such, limiting inflammation during an infection is an essential goal, for which several counter regulatory mechanisms are put into play, like the production of adrenal steroid hormones. This will assure a successful defense and adaptation of the organism to injury, highlighting the relevance of the relationship between adrenal hormones and the immune response. Chronic infections with bacteria, or parasites were found to display several endocrine abnormalities, ranging from subtle disturbances to substantial alterations in the regulation of the HPA axis. Facts accounting for such disturbances encompass several non-mutually exclusive possibilities, inflammation in neuroendocrine tissues, partly due to the presence of pathogens and the ensuing structural and functional alterations; along with the exploitation of the host's hormonal microenvironment by the infectious agent. Alterations in the steroid hormone axis may be also viewed as one of the consequences resulting from the re-directioning of energy to the immune system during chronic infections. Collectively, these alterations further contribute to a deficient control of infection and immunopathology, together with metabolic changes, which promote an unsuitable scenario for disease prognosis.
Recent experimental and clinical evidence has suggested a synergistic causal role among adipose tissue hypertrophy, dyslipidemia, and systemic inflammation in the development and instability of the atherosclerotic plaque. Here, we summarize some of the most recent findings regarding the role of white adipose tissue hypertrophy in the development of dyslipidemia and chronic low-grade systemic inflammation. We also review the contribution of dyslipidemia in releasing free-fatty acids, cholesterol, and oxidized low-density lipoproteins as metabolic ligands able to trigger inflammatory signal pathways in macrophages via pattern recognition receptor (PRR) activation. Finally, we discuss the possible mechanisms through which dyslipidemia-related metabolic ligands and chronic low-grade systemic inflammation are capable of inducing macrophage activation, which in turn is involved in mediating instability and rupture of the atherosclerotic plaque. A better understanding of the inflammatory mechanisms contributing to atherosclerosis may help to identify potential molecular targets to decrease the cardiovascular risk in patients by using anti-inflammatory therapies and PRR blockers.
Thymus is the central organ of immunity, which has a decisive role in the selection and removal of the autoreactive lymphocytes. The pineal gland influences the sustenance and function of thymus, the neonatal removal of thymus as well as pineal gland causes the total collapse of the immune system. Involution of pineal and/or thymus after adolescence permits the manifestation of autoimmune processes, causing the aging and determining the lifespan. Thymus involution is not a consequence of the general involution caused by the progressing age, but a prime mover of it. The pacemaker of aging could be in the suprachiasmatic nucleus of the brain, which is in neural and chemical contact with the the pineal body and the executor is the thymus, regulating the autoimmunity. From this aspect aging is caused by the continuous slow wearing of cells and organs by autoimmunity. A certain degree of autoimmunity is a natural process, which causes manifest disease if becomes enormously strong or directed towards a special organ or system. The velocity of the slow wearing as well, as the functional importance of the target organs determines the lifespan. Outer factors can not prolong the lifespan however, can shorten it by increasing thymic involution, consequently influencing autoimmunity.
