Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: Future therapeutic targets

ArticleinEuropean Journal of Pharmacology 585(2-3):361-74 · June 2008with18 Reads
DOI: 10.1016/j.ejphar.2008.02.095 · Source: PubMed
Abstract
The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory bowel disease and irritable bowel syndrome. Since both disorders are associated with increased immune cell numbers, nerve growth and activation of both immune cells and nerves, we focus in this review on the involvement of immune cell-nerve interactions in inflammatory bowel disease and irritable bowel syndrome. Firstly, the possible effects of enteric nerves, especially of the nonadrenergic and noncholinergic nerves, on the intestinal immune system and their possible role in the pathogenesis of chronic intestinal inflammatory diseases are described. Secondly, the possible effects of immunological factors, from the innate (chemokines and Toll-like receptors) as well as the adaptive (cytokines and immunoglobulins) immune system, on gastro-intestinal nerves and its potential role in the development of inflammatory bowel disease and irritable bowel syndrome are reviewed. Investigations of receptor-mediated and intracellular signal pathways in neuro-immune interactions might help to develop more effective therapeutic approaches for chronic inflammatory intestinal diseases.
    • "In consequence, compensatory immune reactions are excessively triggered, a process that is believed to finally result in chronic intestinal inflammation [2]. The abnormal influx of immune cells into the mucosa is dependent on an increased expression of cytokines and chemokines and their receptors during IBD [3,4]. Thus, most biological therapy strategies are aimed at neutralization and reduction of these cytokines using specific monoclonal antibodies or soluble receptors via systemic administration [5] . "
    [Show abstract] [Hide abstract] ABSTRACT: Cytokines and chemokines are predominant players in the progression of inflammatory bowel diseases. While systemic neutralization of these players with antibodies works well in some patients, serious contraindications and side effects have been reported. Therefore, the local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach. In this study, we produced multi-shell nanoparticles consisting of a calcium phosphate (CaP) core coated with siRNA directed against pro-inflammatory mediators, encapsulated into poly(d,l-lactide-co-glycolide acid) (PLGA), and coated with a final outer layer of polyethyleneimine (PEI), for the local therapeutic treatment of colonic inflammation. In cell culture, siRNA-loaded CaP/PLGA nanoparticles exhibited a rapid cellular uptake, almost no toxicity, and an excellent in vitro gene silencing efficiency. Importantly, intrarectal application of these nanoparticles loaded with siRNA directed against TNF-α, KC or IP-10 to mice suffering from DSS-induced colonic inflammation led to a significant decrease of the target genes in colonic biopsies and mesenteric lymph nodes which was accompanied with a distinct amelioration of intestinal inflammation. Thus, this study provides evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of intestinal inflammation.
    Article · Dec 2015
    • "The performance effects do not reflect the symptoms of the illness and a more likely mechanism is that they are due to effects of immunological changes on the brain. Cytokine production is a key element in the host's acute phase reaction to infection (Kraneveld et al., 2008 ). A number of behavioural symptoms accompany this acute phase reaction and collectively these are known as sickness behaviour (Hart, 1998; Dantzer, 2004). "
    [Show abstract] [Hide abstract] ABSTRACT: CONTEXT: It has been shown that stress increases susceptibility to the upper respiratory tract illnesses (URTIs) such as the common cold. Compared to healthy individuals, those with URTIs also report reduced alertness and have slower reaction times. OBJECTIVE: The present study investigated whether those with an URTI who had been exposed to stressful events showed greater impairments than either individuals without a cold or those with an illness and low stress exposure. METHODS: A prospective cohort study was conducted. The volunteers (360 young adults) were recruited when healthy and completed questionnaires measuring negative life events, personality and health-related behaviours. They also rated their alertness and performed a simple reaction task. If volunteers developed an upper respiratory illness they returned to the laboratory and completed a symptom check list and had nasal secretion and sub-lingual temperature recorded. They also completed a questionnaire measuring recent daily hassles. Alertness and simple reaction time were also recorded again. Those who did not develop a cold were recalled as controls 12 weeks after the start of the study. Analyses of covariance were carried out comparing colds/no colds and high/low stress groups. Baseline measures were included as covariates. RESULTS: 356 participants completed the study. 120 developed URTIs and 236 were re-tested as controls. The frequency and severity of daily hassles were associated with symptom severity. Alertness was reduced and simple reaction time was slower in the URTIs group and the high stress/ill group showed the biggest impairments. These effects remained significant when health related behaviours and personality were covaried. The difference between the high and low stress URTI groups did not reflect symptom severity. INTERPRETATION: The behavioural impairments induced by the common cold are greater when the person has been exposed to stressful events.
    Full-text · Article · Apr 2013
    • "The performance effects do not reflect the symptoms of the illness and a more likely mechanism is that they are due to effects of immunological changes on the brain. Cytokine production is viewed as a key element in the host's acute phase reaction to infection (Kraneveld et al., 2008 ). A number of behavioural symptoms accompany the acute phase reaction and collectively these are known as sickness behaviour (Hart, 1998; Dantzer, 2004 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Minor illnesses such as the common cold and influenza are frequent and widespread. As well as specific symptoms such as nasal problems and fever, these illnesses are associated with a behavioural malaise. One feature of this malaise is reduced alertness and this has been confirmed using subjective reports and objective measures of performance. Such effects have been obtained with both experimentally induced infections and in studies of naturally occurring illnesses. The mechanisms underlying the effects are unclear but possibly reflect effects of cytokines on the CNS which result in changes in neurotransmitter functioning that lead to reduced alertness. The malaise induced by these illnesses has many real-life consequences and activities such as driving and safety at work may be at risk. These illnesses not only have direct effects on performance and mood but also make the person more sensitive to effects of other negative influences such as noise, alcohol and prolonged work. Countermeasures include ingestion of caffeine and other drugs known to increase alertness.
    Full-text · Article · Sep 2012
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