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Persistent Inflammation (persistent + inflammation)
Selected AbstractsTryptophan metabolism and oxidative stress in patients with Huntington's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 3 2005N. Stoy Abstract Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed that the kynurenine : tryptophan ratio was greater in HD than controls in the baseline state and after tryptophan depletion, indicating increased indoleamine dioxygenase activity in HD. Evidence for persistent inflammation in HD was provided by elevated baseline levels of C-reactive protein, neopterin and lipid peroxidation products compared with controls. The kynurenate : kynurenine ratio suggested lower kynurenine aminotransferase activity in patients and the higher levels of kynurenine in patients at baseline, after depletion and loading, do not result in any differences in kynurenic acid levels, providing no supportive evidence for a compensatory neuroprotective role for kynurenic acid. Quinolinic acid showed wide variations in blood levels. The lipid peroxidation data indicate a high level of oxidative stress in HD patients many years after disease onset. Levels of the free radical generators 3-hydroxykynurenine and 3-hydroxyanthranilic acid were decreased in HD patients, and hence did not appear to contribute to the oxidative stress. It is concluded that patients with HD exhibit abnormal handling of tryptophan metabolism and increased oxidative stress, and that these factors could contribute to ongoing brain dysfunction. [source] Nasal CpG oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individualsALLERGY, Issue 9 2009A. Månsson Background:, We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods:, Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results:, Increased NAR, nasal NO production and secretion of interleukin (IL)-1,, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion:, Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response. [source] Perspectives on cancer immuno-epidemiologyCANCER SCIENCE, Issue 12 2004Kei Nakachi Estimating human cancer risk based on host-environment interaction is one task of epidemiology, and it has provided indispensable knowledge for prevention of cancer. The recent development of gene-engineered mice has also provided solid evidence about the relationship between cancer development and immunity. The aim of this review is to discuss the possible contribution of epidemiology to understanding the role of immunity in host defense against cancer, and also to assess the involvement of inflammation in the occurrence of selected cancers. Here we look at the concepts of cancer immunosurveillance and infection-inflammation-cancer, and include a brief introduction to recent studies in humans and experimental animal models. It has been postulated for many years that the immune system has the ability to recognize and eliminate nascent transformed cells in the body (so-called cancer immunosurveillance hypothesis), and this idea has recently obtained strong support from animal experiments. In humans, follow-up studies among immunosuppressed transplant recipients revealed a remarkably increased risk of not only selected malignancies, but also cancers with no known viral etiology. On the other hand, a prospective cohort study among the general population revealed that individuals with low natural cytotoxic activity of peripheral blood lymphocytes had an increased risk of cancer development. More studies are warranted to allow the construction of a model for the interaction between host immunity, aging, and the environment. The host immune system is also involved in inflammatory responses to pathogen infection: insufficient immune function of the host, or repeated infection, may result in persistent inflammation, where growth/ survival factors continuously act on initiated cells. The combined use of biomarkers will be necessary to define low-grade persistent inflammation in future cohort studies; and, in addition to these phenotype marker-based cohort studies, one plausible future direction will be a genomic approach that can be undertaken within cohort studies, looking at the genetic background underlying individual variations in phenotype markers. [source] Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipperCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2009X-H. Zhang Summary Background Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. Objective Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-,, IL-4, IL-13, IL-1,, and TNF-, on GILZ mRNA expression in normal sinonasal mucosa. Results The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1,, TNF-,, IL-4, and IL-13 reduced, whereas IFN-, enhanced GILZ mRNA levels in the sinonasal mucosa. Conclusion Down-regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines. [source] Systemic anti-inflammatory fibrosis suppression in threatened trabeculectomy failureCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2004Brendan Vote FRANZCO Abstract Purpose:,To provide a rationale for the use of systemic anti-inflammatory fibrosis suppression in the postoperative management of threatened early trabeculectomy bleb failure. Methods:,A review of the literature and of the authors' own experiences was conducted. Results:,The most important cause of persistent elevation of intraocular pressure after trabeculectomy is unduly marked or persistent inflammation with deposition of fibrous tissue, which prevents the formation of an adequately draining bleb. It was found that a clinically useful degree of suppression of bleb inflammation and fibrosis can be obtained with a 4,6 week course of the combined systemic administration of prednisone (10 mg t.i.d.), a non-steroidal anti-inflammatory agent (e.g. diclofenac 100 mg SR daily) and colchicine (0.25 mg or 0.3 mg t.i.d.), which was termed anti-inflammatory fibrosis suppression. Topical atropine 1% t.i.d. and adrenaline 1% t.i.d. eye drops can also be considered in addition to routine postoperative topical steroids. Conclusions:,Despite advances in surgical techniques and methods to control fibrosis, anti-inflammatory fibrosis suppression is a valuable tool to have available in the postoperative period for management of trabeculectomies that threaten failure. This regime produces a diffuse bleb, which has a very low risk of late infection or bleb perforation. It is recommend that this regime be added to the list of therapies that are considered when clinical features suggestive of a failing bleb are confronted early in the postoperative course. [source] | ||||||||||