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At least 595 records · Page 33Linked to original sources
PubMed2006

Substance P receptor mediated maintenance of chronic inflammation in EAE.

Substance P (SP) is a modulatory, pro-inflammatory neuropeptide. We investigated the role of the SP receptor, neurokinin-1 (NK-1), in EAE. Our data show that in the chronic phase, mice lacking NK-1 have improved mobility and decreased numbers of LFA-1 high CD4+ T cells and MOG-specific, IFN-gamma producing CD4+ T cells. SR140333, an NK-1 antagonist, administered alone during the chronic phase of EAE was not sufficient to ameliorate symptoms. These results indicate that SP, through NK-1, contributes to maintenance of CNS inflammation, and combining NK-1 antagonists with conventional anti-inflammatory treatments may enhance the success of treatments for diseases like multiple sclerosis.

Animals↗
PubMed2006

Interferon-gamma down-regulates transcription of the mu-opioid receptor gene in neuronal and immune cells.

Earlier investigations demonstrated up-regulated mu-opioid receptor expression in neuronal and immune cells in response to IL-1, IL-4, IL-6 and TNF-alpha. We herein report that mu-opioid receptor expression is down-regulated in SH SY5Y neuroblastoma cells by IFN-gamma, and that IL-4-mediated induction of mu-opioid receptor expression is inhibited in Jurkat T cells by IFN-gamma. Additionally, mu-opioid receptor transcripts were found in IL-4-expressing human primary T helper cells type 2, but not in type 1 cells, which typically express IFN-gamma. This indicates that mu-opioid receptor expression may be altered under conditions like inflammation, viral infections or neurological diseases associated with imbalanced cytokine expression.

Down-Regulation↗
PubMed2006

Effects of acute or chronic omega-3 and omega-6 polyunsaturated fatty acid treatment on behavioral, neuroendocrine and cytokine changes elicited by exogenous interleukin-1beta challenge.

Chronic omega-3 or omega-6 polyunsaturated fatty acid (n-3; n-6 respectively) treatment attenuated human interleukin-1beta (hIL-1beta; 5.0 microg/kg)-elicited rise of circulating ACTH levels and attenuated the sickness behavior and locomotor suppression elicited by the cytokine. Furthermore, hIL-1beta markedly elevated circulating levels of plasma IL-6, an effect attenuated by n-3, but not n-6 treatment. Such protective effects were not evident upon short-term (3 day) n-3 exposure. These results demonstrate that long-term administration of either n-3 or n-6 confers protection against several neuroendocrinological, immunological and behavioral actions of hIL-1beta challenge, although in general the effects of n-3 were more pronounced.

Adrenocorticotropic Hormone↗
PubMed2006

In vivo modulation of LPS-induced alterations in brain and peripheral cytokines and HPA axis activity by cannabinoids.

This study investigated cannabinoid receptor-mediated regulation of brain and peripheral cytokines in vivo. The cannabinoid receptor agonist, HU210 attenuated lipopolysaccharide (LPS)-induced increases in IL-1beta and TNFalpha in rat brain and IL-1beta, TNFalpha, IL-6 and IFNgamma in plasma. The CB(1) receptor antagonist, SR141716A, attenuated the immunosupressive effects of HU210 on IL-1beta, but not TNFalpha. SR141716A or the CB(2) receptor antagonist, SR144528, alone attenuated LPS-induced cytokine increases. LPS and/or cannabinoids also reduced circulating lymphocyte numbers and increased corticosterone levels. These data provide evidence for modulation of pro-inflammatory cytokines in vivo by cannabinoid receptors and inform the development of cannabinoids for neuroinflammatory disorders.

Animals↗
PubMed2006

Interleukin-1beta and interleukin-6 stimulate matrix metalloproteinase-9 secretion in cultured myenteric glia.

Western blotting of culture media of myenteric glia stained positive for GFAP revealed increased secretion of matrix metalloproteinase-9 (MMP-9) in interleukin-1beta (IL-1beta) stimulated cells (10 ng/mL) versus control (142 +/- 19 versus 42 +/- 19, P < 0.05). Interleukin-6 (IL-6) stimulated cells also showed increased expression of MMP-9 (10 ng/mL) versus control (69 +/- 14 versus 4 +/- 2, P < 0.01). Control and cytokine-stimulated cells secreted MMP-2 constituitively. Gelatin zymography demonstrated that products were biologically active. Cytoplasmic staining for MMP-9 was detected in IL-1beta and IL-6-stimulated cells but was negligible in controls. Cultured myenteric glia are responsive to IL-1beta and IL-6 stimulation by secreting MMPs into the extracellular environment.

Animals↗
PubMed2004

Psychoneurodendocrine correlates of lymphocyte subsets during healthy ageing.

Ageing has been associated with increased cortisol levels and absolute counts of T lymphocytes with memory phenotype. Although the mechanisms underlying these changes are still unknown, it has been speculated that this could be related to a dysfunction in FAS/CD95 expression in naive or memory cells. In this study, we investigated the role of psychoneuroendocrine variables in regulating CD95 expression on lymphocyte subsets. Forty-six elderly subjects (65-91 years) and 33 young adults (20-40 years) were recruited accordingly the SENIEUR protocol. The psychological status was measured by structured clinical interviews, salivary cortisol was assessed along the day (9, 12 and 22h) and peripheral blood lymphocytes were immunophenotyped. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased in the elderly, indicating an activation of the hypothalamic-pituitary-adrenal (HPA) axis. We observed reduced counts of CD45RA+CD95+ cells in the elderly compared to young adults. The elderly subjects also showed a reduced expression of CD3 and CD62L in contrast to increased CD95 expression in CD45RA+ cells. The emotional state was positively correlated with the lymphocyte markers. Our data suggest the healthy ageing is associated with psychoneuroendocrine alterations that may be implicated in the regulation of CD95 expression on peripheral T cells.

Aged↗
PubMed2004

Is fibromyalgia an autoimmune disorder of endogenous vasoactive neuropeptides?

Fibromyalgia (FM) is a disorder characterised by soft tissue pain, disturbance of function an often prolonged course and variable fatigue and debility. A clearly defined aetiology has not been described. This paper proposes that immunological aberration is likely and this may prove to be associated with an expanding group of novel vasoactive neuropeptides. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault and the maintenance of homeostasis. Failure of these substances has adverse consequences for homeostasis. This paper describes a biologically plausible mechanism for the development of FM based on loss of immunological tolerance to the vasoactive neuropeptides. The proposed mechanism of action is that inflammatory cytokines are provoked by tissue injury from unaccustomed exercise or physical injury. This may trigger a response by certain vasoactive neuropeptides which then undergo autoimmune dysfunction as well as affecting their receptor binding sites. The condition may potentially arise de novo perhaps in genetically susceptible individuals. FM is postulated to be an autoimmune disorder and may include dysfunction of purine nucleotide metabolism and nociception.

Autoimmune Diseases↗
PubMed2004

Is sudden infant death syndrome (SIDS) an autoimmune disorder of endogenous vasoactive neuropeptides?

Sudden infant death syndrome (SIDS) remains a perplexing diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. Investigations into the endogenous vasoactive neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are revealing the critical role these substances have in homeostasis including thermo- and cardiovascular regulation. For example, studies in PACAP receptor-deficient mice have revealed sudden neonatal death attributed to respiratory control defects, possibly due to mutations in genes encoding components of PACAP signalling pathways. PACAP and VIP belong to the secretin/glucagon superfamily of hormones and function as vasoactive neuropeptides. They act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides have a known role in thermoregulation and deficiency states are associated with higher neonatal death rates in rats. PACAP plays a significant role in carbohydrate and lipid metabolism and impairment of functioning has potentially serious consequences. It is postulated PACAP and VIP receptors in brain may become compromised through autoimmune phenomena resulting in cardio-respiratory dysfunction and death. This paper discusses the potential role of certain vasoactive neuropeptides in causing autoimmune responses in susceptible infants predisposing them to SIDS.

Autoimmune Diseases↗
PubMed2004

Is osteoporosis linked to vaccinations and Gulf War Syndrome?

Gulf War Syndrome (GWS) remains a contentious diagnosis with conflicting laboratory investigations and lack of a biologically plausible aetiology. Assertions have been made that GWS may be the result of vaccinations given to serving military personnel in the Persian Gulf and may be associated with osteoporosis. Calcitonin gene related protein (CGRP) is a vasoactive neuropeptide that is synthesised in conjunction with calcitonin gene expression. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. This paper describes a biologically plausible mechanism for the development of osteoporosis in the context of GWS based on loss of immunological tolerance to the vasoactive neuropeptide CGRP or its receptors following a variety of antigenic events.

Autoimmune Diseases↗
PubMed2004

Is Gulf War Syndrome an autoimmune disorder of endogenous neuropeptides, exogenous sandfly maxadilan and molecular mimicry?

Gulf War Syndrome (GWS) remains a contentious diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. This paper discusses the potential role of maxadilan, a potent sandfly vasoactive peptide, in causing autoimmune responses in susceptible individuals through possible molecular mimicry with pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1R receptor. Gulf War Syndrome may share some causative pathology with Chronic Fatigue Syndrome (CFS), a disorder characterised by prolonged fatigue and debility mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory has been recently raised as possible cause of CFS. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Maxadilan, while not sharing substantial sequence homology with PACAP is a known agonist of the PACAP specific receptor (PAC1R) and therefore emulates these functions. Moreover a specific amino acid sequence peptide deletion within maxadilan converts it to a PACAP receptor antagonist raising the possibility of this substance provoking a CFS like response in humans exposed to it. This paper describes a biologically plausible mechanism for the development of a GWS-like chronic fatigue state based on loss of immunological tolerance to the vasoactive neuropeptide PACAP or its receptor following bites of the sandfly Phlebotomus papatasi and injection of the vasodilator peptide maxadilan. Exacerbation of this autoimmune response as a consequence of recent or simultaneous multiple vaccination exposures deserves further investigation. While the possible association between the relatively recently discovered vasoactive neuropeptides and chronic fatigue conditions has only recently been reported in the literature, this paper explores links for further research into GWS and CFS.

Autoimmune Diseases↗
PubMed2004

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

Autoimmune Diseases↗
PubMed2004

Does neuroimmune dysfunction mediate seasonal mood changes in winter depression?

BACKGROUND: Animal studies have demonstrated seasonal changes in immune function mediated by nocturnal melatonin duration as a biological signal for photoperiod. Recent research has highlighted the potential role of neuroimmune dysfunction in depressive disorders. The etiology of winter depression (seasonal affective disorder, or SAD) is not known, but a number of studies have provided support for both photoperiod and neurotransmitter hypotheses. HYPOTHESIS: A new hypothesis is presented that links the SAD data on melatonin, photoperiod, and neurotransmitters by proposing that seasonal increases in proinflammatory cytokines are critical in the pathophysiology of winter SAD. TESTING THE HYPOTHESIS: In SAD patients, but not healthy subjects: proinflammatory cytokines will be increased and the Th1/Th2 balance will be shifted to the left in winter compared to summer; neuroimmune function will be correlated with nocturnal melatonin duration in SAD patients; and light treatment will correct neuroimmune dysfunction. IMPLICATIONS OF THE HYPOTHESIS: Diagnostic tests for SAD may be developed using cytokine assays; neuroimmune dysfunction may be predictors of response to treatments; new treatments for SAD (immune or anti-inflammatory treatment) may be developed.

Animals↗
PubMed2005

Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders?

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism. The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.

Autoimmune Diseases↗
PubMed2006

Possible interactions of genetic and immuno-neuro-endocrine regulatory mechanisms in pathogenesis of congenital anomalies.

The process of organogenesis depends on genetic and environmental factors. Besides genetic background, congenital anomalies can also be influenced by micro environmental changes, which are related to maternal-foetal interactions followed by the production of cytokines, hormones, neurotransmitters, growth factors and biochemical mediators, and stress proteins. Pre-natal maternal stress, including infections, psychological stress and other teratogens, can influence a disregulation of maternal immune, endocrine and nervous systems, during pregnancy. This is a crucial condition for the abnormal growth and development of the foetus. Activated maternal immune system can alter the cytokine network and make it inadequate for normal embryogenesis and organogenesis. Heat-shock proteins play an important role in stress physiology repairing DNA errors or activating pro-inflammatory response. Regarded from this aspect, the altered cytokine network suggests aetiopathogenetic basis of congenital anomalies in neonates. It is our wish to point out our potentially harmful conditions in the development of congenital anomalies, as well as their control by using pre-natal and pre-conceptional diagnostics and treatment.

Animals↗
PubMed2005

Cytokine mRNA levels in brain and peripheral tissues of the rat: relationships with plus-maze behavior.

There is evidence that interleukin (IL)-2 may be related to anxiety as measured in the elevated plus-maze. Recently, we showed that normal adult male Wistar rats can differ systematically in this test of avoidance behavior, that is, time spent on the open arms of the elevated plus-maze. Rats with low open arm time had higher striatal levels of IL-2 mRNA than those with high open arm time, but did not differ significantly in expression of other striatal cytokine mRNA. Here, we investigated whether these expression effects are anatomically specific to the striatum. Therefore, we asked in this double-blind study whether elevated plus-maze behavior may also be related to endogenous levels of cytokine mRNA in other brain regions, which play a role for anxiety, namely the amygdala, hippocampus, and the prefrontal cortex. Additionally, and as peripheral controls, immuno-neuro-endocrine relevant tissues (adrenal glands, spleen) were analyzed. Based on open arm time in the elevated plus-maze, male Wistar rats were divided into sub-groups with either low or high open arm time behavior. Then, IL-1beta, IL-2, IL-6, and tumor necrosis factor (TNF)-alpha cDNA levels were measured post-mortem using semi-quantitative, competitive, reverse transcription polymerase chain reaction. First, we found that cytokine expressions differed considerably between and within these central and peripheral tissues. Secondly, rats with high compared to low open arm time behavior showed higher IL-2 mRNA levels in the prefrontal cortex, which is an inverse pattern to what we recently found in the striatum. These results provide new evidence indicating that cytokine mRNA in the brain can be related to elevated plus-maze behavior and that this relationship is site (prefrontal cortex, striatum)- and cytokine mRNA-specific (IL-2).

Adrenal Glands↗
PubMed2004

Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy.

In the present study, the expression of pro-inflammatory transcripts was assessed across the brain of mice having undertaken pilocarpine-induced seizures. Pilocarpine-induced marked neurodegeneration and demyelination in multiple regions of the forebrain. The pattern of genes encoding toll-like receptor type 2 (TLR2) and I kappa B alpha (index of NF-kappa B activation) was associated with the neurodegenerating areas, but this was not the case for the mRNA encoding other inflammatory proteins. Scattered tumor necrosis factor-alpha (TNF-alpha)-expressing cells were found across brain, whereas the signals for monocyte-chemoattractant protein-1 and microsomal prostaglandin mPGES E synthase were robust in thalamus and cerebral cortex and weak in the hippocampus and amygdala. TLR2 and TNF-alpha transcripts were expressed mainly in microglia/macrophages. Cyclooxygenase-2 was induced specifically in the hippocampus and piriform cortex. A low increase in interleukin-12 mRNA was detected in the brain, but the signal for interferon gamma (IFN-gamma) remained undetectable. Although pro-inflammatory markers were induced in a different manner across the CNS, their patterns were not characteristic of those caused by other inflammatory challenges, such as endotoxin. These data suggest a different mechanism involved in regulating the innate immune reaction in response to seizures and could have direct implications for the neuropathology associated with epilepsy.

Animals↗