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PubMed1984

A model of persistent antigen-induced chronic inflammation in the rat air pouch.

Continuing antigen-induced inflammation was established in a subcutaneous air pouch in rats by recurrent local challenge. The animals were sensitized using bovine serum albumin in Freund's complete adjuvant and were challenged 14 days later by injection of the antigen in a solution containing sodium carboxymethylcellulose into the air pouch to produce allergic inflammation. A single antigenic challenge induced acute inflammation with a predominantly polymorph infiltration in the first 48 h. Later samples showed a low-grade mononuclear response which persisted for 4-5 days. Repeated challenge produced chronic inflammation with an accentuated mononuclear response. Connective tissue activation involving fibronectin and collagen was seen as the inflammation progressed, and this was associated with production of ferritin by mononuclear cells. Discontinuation of challenge injections resulted in resolution of the granuloma. We suggest this model can be used to investigate the mechanisms involved in chronic inflammatory diseases with an immunological component and to evaluate the effects of therapeutic intervention upon chronic allergic inflammation.

Animals↗

PubMed1996

Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops.

OBJECTIVE: The development of bronchopulmonary dysplasia (BPD) often has been attributed to injury from mechanical ventilation and supplemental oxygen. Early lung inflammation in infants with BPD has been thought to be secondary to these factors. The purpose of this study was to evaluate whether preexisting (prenatal) inflammation may be a primary causative factor in the development of BPD. METHODS: Intubated newborns of less than 2,000 g birth weight were prospectively enrolled. The presence or absence of chorioamnionitis was documented. Lung inflammation was evaluated on days 1, 2, and 4 of intubation by assaying concentrations of interleukin 1 beta (IL-1 beta), thromboxane B2, leukotriene B4, and prostaglandin E2 in tracheal lavages. Infants in whom BPD developed were compared with those in whom it did not using these measures. RESULTS: Fifty-three infants were enrolled; 41 survived. Thirty-eight had respiratory distress syndrome; 15 were intubated for other diagnoses. Infants prenatally exposed to chorioamnionitis were less likely to present with respiratory distress syndrome; however, chorioamnionitis was significantly associated with both the presence of IL-1 beta from the first day of intubation and the development of BPD. Tracheal lavage concentrations of IL-1 beta were higher in infants in whom BPD developed. Thromboxane B2 concentrations were similar on day 1 but were higher on days 2 and 4 in infants in whom BPD developed. CONCLUSIONS: In this study, intubated infants weighing less than 2,000 g at birth in whom BPD developed had increased exposure to inflammation prenatally (chorioamnionitis) and evidence of increased lung inflammation from the first postnatal day. We speculate that chorioamnionitis may accelerate lung maturation but that it also causes lung inflammation and subsequent lung injury in intubated infants, fostering the development of BPD.

Bronchoalveolar Lavage↗

PubMed1996

Pollinosis etiologic relationship between excessive IL-4 production and down-regulation of the inflammation-suppressive system.

Previous findings suggest a bi-directional relationship between the immune and endocrine systems, which may expand to a major inflammation-regulatory mechanism, although its mechanism is largely unknown, especially in the human body. Lymphokine and neuroendocrine peptide hormones have been identified as two major groups of immunologic mediators. The particularly pivotal molecules among them are interleukin (IL-1), considered to be a mediator of inflammation, and ACTH, whose activation is induced by IL-1. Among the important functions of lymphokines related to atopic inflammation is the regulation of IgE secretion from B cell through the action of IL-4, produced from the Th2 subset stimulated by IL-1, as a switch factor. IL-4 is the major IgE secretagogue. IL-4 is, moreover, a potent suppressive stimulant of IL-1 secretion. In this study, we tested the hypothesis whether a immunologic interaction exists in patients with allergic rhinitis to Japanese cedar pollen. We performed immunohistochemical staining of IL-1 beta, interleukin 1 receptor (IL-1r) and interleukin-4 (IL-4) in the nasal tissue, and evaluated serum levels of the biochemical mediators involved in the inflammation-regulatory mechanism: IL-1 beta, IL-4, interleukin 1 receptor antagonist (IL-1ra), IgE, cortisol, and ACTH before, during, and after allergen-provoked rhinitis in pollinosis sufferers. Our morphological study showed that, even before the pollen season, large amounts of IL-4 and IL-1r, exclusive of IL-1 beta, were produced in the nasal tissue of patients with seasonal pollinosis. IL-1-positive cells were observed in small amounts in the same tissue, but the quantity was probably enough to cause secretion of intrinsic IL-4 to produce sufficient IgE for atopic inflammation. Upon immunoenzymatic measurement of serum IL-4, even before the pollen season, almost all atopic patients also showed a higher IL-4 level than controls. Serum IgE data also showed a high level before the pollen season in atopic patients. This evidence suggests that atopic patients have already set the first step of inflammatory event not only in the nasal epithelium but also generally even before inhaling proper quantity and quality of the allergen. On the other hand, although atopic patients had inflammation, they did not show an extremely high value of serum IL-1, regarded as inflammatory lymphokine, compared with non-atopic individuals. In contrast, a higher serum level of IL-1ra was observed before and during the pollen season in atopic patients, subsiding to normal level after the season. Serum levels of both cortisol and ACTH did not show a high value in atopic patients during the season. These results demonstrate that excessive IL-4 production of atopic patient causes down-regulated transformation of IL-1 and up-regulated secretion of IL-1ra generally, followed by failure to increase secretion of ACTH from hypophysis and cortisol generally, resulting in defective performance of a specifically useful function of the anti-inflammatory mechanism.

Adrenocorticotropic Hormone↗

PubMed1998

Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice.

Asthma is characterized by chronic eosinophilic inflammation of the airways, and allergen-specific Th2 lymphocytes are thought to play a major role in the development and maintenance of this type of inflammation in allergic asthma. It is generally accepted that airway dendritic cells (DC) are essential for stimulating naive T cells in a primary immune response to inhaled Ag and for the development of allergic sensitization. We have examined the role of airway DC in stimulating memory T cells in a secondary response to inhaled Ag and the subsequent development of chronic airway inflammation. In our mouse model of asthma, OVA aerosol challenge in OVA-sensitized mice leads to CD4-dependent peribronchial and perivascular eosinophilic inflammation, lung Th2 cytokine production, and systemic IgE production. We have used conditional depletion of airway DC by treatment of thymidine kinase-transgenic mice with the antiviral drug ganciclovir to deplete DC during the secondary exposure to OVA. In sensitized thymidine kinase-transgenic mice, a significant decrease in the number of bronchoalveolar CD4 and CD8 T lymphocytes and B lymphocytes was seen after ganciclovir treatment. In addition, Th2 cytokine-associated eosinophilic airway inflammation was almost completely suppressed. These studies demonstrate for the first time that the DC is essential for presenting inhaled Ag to previously primed Th2 cells in the lung, leading to chronic eosinophilic airway inflammation. Altering the function of airway DC may therefore be an important target for new anti-asthma therapy.

Administration, Inhalation↗

PubMed1998

The role of T cells in polyethylene particulate induced inflammation.

OBJECTIVE: To investigate the role of T lymphocytes in ultra-high molecular weight polyethylene (UHMWPE) induced inflammation in joint arthroplasty. METHOD: We address the role of T cells in wear induced inflammation by injecting the knee joints of both immune competent rats and mice and severe combined immunodeficient (SCID) mice with UHMWPE. Histological and immunohistochemical analysis of the synovial tissues was compared. Interaction between human T cells and UHMWPE particles was examined in vitro using T cell activation assays. RESULTS: Histological and immunohistochemical analysis of the knees of the immune competent animals showed significant UHMWPE induced inflammation. In contrast, the tissue in the SCID mice knee joints showed very little inflammatory response to UHMWPE despite phagocytosis of the particulate. Since the SCID mice have no functional T or B lymphocytes, it is highly likely that the lack of inflammation in knee joints may be due to the absence of mouse T cells, as the infiltration of T cells into the joint tissue may enhance the inflammatory response to UHMWPE particles. T cell activation assays showed that T cells were not directly activated by UHMWPE particles and the nature of the interaction was not revealed from these experiments. CONCLUSIONS: Although T cells are not directly involved in UHMWPE particle induced inflammation, as shown by the T cell activation assays, the histological data from the mice studies clearly show differences in the amplitude of inflammation from animals with and without functional T cells. Our studies suggest that the T cells may enhance the inflammatory response due to a bystander effect. Since the macrophages upon ingestion of UHMWPE particles release several cytokines including tumor necrosis factor-alpha, interleukin 1, and IL-6, it is possible that T cells in the vicinity of these macrophages may become attracted to the knee joint and activated due to cytokine release.

Animals↗

PubMed1998

Changes in colonic inflammation induced by dextran sulfate sodium (DSS) during short- and long-term administration of rebamipide.

Earlier studies have shown the antiinflammatory effects of histamine and nitric oxide (NO) in a model of colitis induced by DSS. However, the defense system against free radicals in this model remained unclear. The aim of this study was to evaluate the effects of rebamipide, which inhibits the production of free radicals, in this model using male Sprague-Dawley rats. Colitis induced by 1% DSS is characterized by slow, weak inflammation and is regarded as a chronic inflammation model. In contrast, colitis induced by 4% DSS is characterized by fast, strong inflammation and is regarded as the acute inflammation model. Endoscopic examinations, peripheral white blood cell (WBC) counts, and assays of myeloperoxidase activity (MPO) in homogenates of colon mucosa were performed after one week (4% DSS model) and eight weeks (1% DSS model). Inflammation of colon mucosa was milder in the rats given rebamipide compared with controls in both the 4% and 1% DSS model. Furthermore, peripheral WBC counts correlated with colonic MPO activity. These findings indicate that rebamipide works as an antiinflammatory agent in both acute and chronic inflammation.

Acute Disease↗

PubMed2006

Systemic inflammation in heart failure--the whys and wherefores.

Patients with chronic heart failure (HF) are characterized by systemic inflammation, as evident by raised circulating levels of several inflammatory cytokines with increasing levels according to the degree of disease severity. In addition to the myocardium itself, several tissues and cells can contribute to this inflammation, including leukocytes, platelets, tissue macrophages and endothelial cells. Although the mechanisms for the systemic inflammation is unknown, both infectious (e.g., endotoxins) and non-infectious (e.g., oxidative stress and hemodynamic overload) events could be operating, also including activation of Toll-like receptors as well as interaction with the neurohormone system. A growing body of evidence suggests that this systemic inflammation in chronic HF may play a role in the development and progression of this disorder, not only by promoting myocardial dysfunction, but also by inducing pathogenic consequences in other organs and tissues, thereby contributing to additional aspects of the HF syndrome such as cachexia, endothelial dysfunction and anemia. Although this inappropriate immune activation and inflammation could represent a new target for therapy in patients with chronic HF, the anti-tumor necrosis factor trials have been disappointing, and future research in this area will have to more precisely identify the most important mechanisms and actors in the immunopathogenesis of chronic HF in order to develop better immunomodulating agents for this disorder.

Anemia↗

PubMed2006

Effects of peripheral inflammation on activation of p38 mitogen-activated protein kinase in the rostral ventromedial medulla.

In the present study, the activation of p38 mitogen-activated protein kinase (p38 MAPK) in the rostral ventromedial medulla (RVM) following the injection of complete Freund's adjuvant (CFA) into the rat hindpaw was examined in order to clarify the mechanisms underlying the dynamic changes in the descending pain modulatory system after peripheral inflammation. Phospho-p38 MAPK-immunoreactive (p-p38 MAPK-IR) neurons were observed in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (GiA). Inflammation induced the activation of p38 MAPK in the RVM, with a peak at 30 min after the injection of CFA into the hindpaw, which lasted for 1 h. In the RVM, the number of p-p38 MAPK-IR neurons per section in rats killed at 30 min after CFA injection (19.4+/-2.0) was significantly higher than that in the naive group (8.4+/-2.4) [p<0.05]. At 30 min after CFA injection, about 40% of p-p38 MAPK-IR neurons in the RVM were serotonergic neurons (tryptophan hydroxylase, TPH, positive) and about 70% of TPH-IR neurons in the RVM were p-p38 MAPK positive. The number of p-p38 MAPK- and TPH-double-positive RVM neurons in the rats with inflammation was significantly higher than that in naive rats [p<0.05]. These findings suggest that inflammation-induced activation of p38 MAPK in the RVM may be involved in the plasticity in the descending pain modulatory system following inflammation.

Adjuvants, Immunologic↗

PubMed2025

Association of Lung Quantitative CT Scan Textures With Systemic Inflammation and Mortality in COPD.

BACKGROUND: COPD is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles (BVBs), which may lead to poor quality of life. Quantitative CT (QCT) scan textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity. RESEARCH QUESTION: Are BVB textures, obtained from the adaptive multiple feature method, associated with systemic inflammation, morbidity, and mortality in COPD? STUDY DESIGN AND METHODS: We analyzed data from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; n = 2,981) and the Genetic Epidemiology of COPD (COPDGene) study (n = 10,305). The predictors included 2 QCT scan biomarkers, the BVB and CT density gradient (CTDG) textures, age, sex, BMI, race, smoking status, pack-years of smoking, CT scan-detected emphysema, and square root of the wall area of a hypothetical airway with a 10-mm lumen perimeter (Pi10). Outcomes included plasma biomarker concentrations from Meso Scale Discovery proteomics assays and CBC counts, both as markers of inflammation, along with FEV1, FEV1 to FVC ratio, St. George's Respiratory Questionnaire score, 6-minute walk distance, and modified Medical Research Council dyspnea scale score. Associations of these QCT scan textures with FEV1 decline and all-cause mortality also were investigated. RESULTS: Increased BVB texture was associated significantly with elevated neutrophil and monocyte counts and the neutrophil to lymphocyte ratio, independent of clinical covariates, CT scan-detected emphysema, and Pi10. Elevated CTDG was associated with increased neutrophil count, NLR, and tumor necrosis factor α. Increased CTDG and BVB textures also were associated with a lower FEV1 and 6-minute walk distance. CTDG at baseline was also associated with decline in FEV1 at the 5-year follow-up in the COPDGene study. We observed a significant association of both BVB texture (SPIROMICS: hazard ratio [HR], 1.084 [95% CI, 1.035-1.135; P < .001]; COPDGene: HR, 1.106 [95% CI, 1.080-1.131; P < .001]) and CTDG texture (SPIROMICS: HR, 1.033 [95% CI, 1.003-1.064; P = .03]; COPDGene: HR, 1.079 [95% CI, 1.061-1.096; P < .001]) with all-cause mortality independent of CT scan-detected emphysema and Pi10. INTERPRETATION: QCT scan textures may provide imaging evidence of the spatial heterogeneity of lung inflammation and overall disease burden in COPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene); URL: www. CLINICALTRIALS: gov.

Humans↗

PubMed2004

Inflammation markers and erythrocyte sedimentation rate but not metabolic syndrome factor score predict coronary heart disease in high socioeconomic class males: the HDDRISC study.

OBJECTIVE: To evaluate prediction of coronary heart disease (CHD) by quantitative measures of the metabolic syndrome and inflammation in a cohort of high socio-economic status males. METHODS: Incident CHD was identified in a cohort of 649 male participants in a company health programme during a mean follow-up of 10.6 years. Using factor analysis, metabolic syndrome and sub-clinical inflammation scores were derived from baseline measurements, which included an oral glucose tolerance test-derived measure of insulin resistance. Factor scores were then included as predictor variables in a Cox regression analysis of incident CHD. RESULTS: Forty-two cases of definite CHD were identified on follow-up. The conventional risk factors, cigarette smoking, blood pressure, total cholesterol and low HDL cholesterol were clearly distinguished as significant predictors of incident CHD. Erythrocyte sedimentation rate was also an independent predictor (coefficient 0.0480, z score 2.39, p=0.017). The metabolic syndrome factor included insulin resistance, body mass index, serum triglycerides, glucose tolerance, serum uric acid and fasting plasma glucose. The inflammation factor included serum globulin, blood leukocyte count, low albumin, haemoglobin and cholesterol, but not erythrocyte sedimentation rate. The inflammation factor score was a significant predictor of CHD (coefficient 0.4601, z score 2.43, p=0.015) but the metabolic syndrome factor was not (coefficient 0.2488, z score 1.24, p=0.2). CONCLUSIONS: Erythrocyte sedimentation rate and a factor analysis-derived measure of sub-clinical inflammation were important in the development of CHD in this relatively low-risk group, but neither metabolic syndrome factor score nor its individual components predicted CHD.

Biomarkers↗

PubMed2005

Novel omega -- 3-derived local mediators in anti-inflammation and resolution.

The integrated inflammatory response of the host is essential in health and disease. Hence, it is important to achieve a more complete understanding of the local cellular and molecular events that govern the formation and actions of local mediators that can serve as endogenous local mediators of resolution. Because these compounds in experimental animal models of inflammation can control the duration and magnitude of inflammation, knowledge of their formation and actions may provide new avenues for appreciating the molecular basis of many inflammatory diseases. The first of these endogenous local counterregulators recognized were the lipoxins, which are trihydroxytetraene-containing mediators generated from arachidonic acid during cell-cell interactions via transcellular biosynthesis. Because this circuit of lipoxin formation appears to be of physiological relevance in resolution, therapeutic modalities targeting this and related systems should allow for the development of novel therapeutic agents (i.e., agonists of the important cellular and physiological responses required for timely resolution). This review offers a general overview of recent advances from studies by the author and colleagues on the biosynthesis and bioactions of the novel anti-inflammatory lipid mediators, resolvins, docosatrienes, and neuroprotectins as well as their endogenous aspirin-triggered epimeric counterparts. These previously unappreciated families of lipid-derived mediators were originally isolated from experimental murine models of acute inflammation captured during the natural spontaneous resolution phase. They possess anti-inflammatory, pro-resolving, and protective properties. Inappropriate resolution mechanism(s) may underlie our current appreciation of the inflammatory phenotype(s) that characterizes many prevalent human diseases where inflammation is now acknowledged to play an important role in the disease process. Moreover, these new pathways give opportunities to appreciate the complex roles of neutrophils in the generation of potent host protective lipid mediators that may be harnessed for the design of novel treatments for a wide range of diseases where inflammation contributes to the pathophysiology of the disorder.

Animals↗

PubMed2002

The association of sensitive systemic inflammation markers with bronchial asthma.

BACKGROUND: Airway inflammation is a characteristic feature of bronchial asthma. Previous studies have shown an increased local inflammatory activity in the airway mucosa of asthma patients. OBJECTIVES: To analyze the association of asthma with three sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A (SAA), and plasma fibrinogen. METHODS: A cross-sectional, population-based study including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic disease risk factor survey in 1997. Of the participating men, 97 were classified as asthma patients. The odds ratios of asthma were analyzed by quartile of each inflammation marker. RESULTS: In logistic regression models the age-adjusted odds ratios (second, third, and fourth quartile as compared with the first quartile) of asthma increased gradually with increasing quartile of C-reactive protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001). The associations were independent of smoking. Further adjustment for waist-to-hip ratio, a marker of central obesity, and symptoms of chronic bronchitis weakened the observed association, but the increasing trend in the association of SAA and fibrinogen with asthma remained highly significant. CONCLUSIONS: Sensitive markers of systemic inflammation, particularly SAA and fibrinogen, were positively and significantly associated with asthma prevalence. These findings support the hypothesis that not only local, but also systemic, inflammation exist in bronchial asthma.

Aged↗

PubMed2003

Chronic inflammation as inductor of pro-cancer microenvironment: pathogenesis of dysregulated feedback control.

Local chronic inflammation can act as a high cancer risk factor. The basis of this pathogenic effect is under investigation. This review examines the evidence that chronic inflammation is capable of inducing the complex of microenvironmental changes similar to those seen around growing cancer cells. The changes include: enhanced oxidative cell resistance against apoptosis; switch to glycolytic metabolism, neovasculogenesis and vasorelaxation which provide nutrient delivery but restrict the immune/inflammatory cell recruiting. These synergistic changes can act as a counter balancing force to self-limit the cytotoxic response by normally acute inflammation. However, the duration and intensity of this force can become insufficient to restrict the prolonged cytotoxic response by chronic inflammation. The hypothetic model of the latter effects is presented as a result of discoordinated feedback regulation among heme-, prostaglandin E2-, nitric oxide-, carbon monoxide-, and polyamine-dependent enzymatic pathways in the growth inhibiting (cytotoxic) and growth promoting (regenerative) stages of acute or chronic inflammatory response. According to this model, chronic inflammation is capable of generating a potentially 'vicious self-sustaining loop(s)' which are resulted in the pro-cancer microenvironment favorable for survival of tumor cells and their growth.

Animals↗

PubMedDate not supplied

Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage.

Inappropriate or prolonged inflammation is the main cause of many diseases; for this reason it is important to understand the physiological mechanisms that terminate inflammation in vivo. Agonists for several Gs-protein-coupled receptors, including cell-surface adenosine purinergic receptors, can increase levels of immunosuppressive cyclic AMP in immune cells; however, it was unknown whether any of these receptors regulates inflammation in vivo. Here we show that A2a adenosine receptors have a non-redundant role in the attenuation of inflammation and tissue damage in vivo. Sub-threshold doses of an inflammatory stimulus that caused minimal tissue damage in wild-type mice were sufficient to induce extensive tissue damage, more prolonged and higher levels of pro-inflammatory cytokines, and death of male animals deficient in the A2a adenosine receptor. Similar observations were made in studies of three different models of inflammation and liver damage as well as during bacterial endotoxin-induced septic shock. We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses.

Adenosine↗

PubMedDate not supplied

Inflammation in end-stage renal disease: sources, consequences, and therapy.

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Although traditional risk factors are common in ESRD patients, they alone may not be sufficient to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor which is commonly observed in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is not yet any recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in these patients.

Cardiovascular Diseases↗

PubMed2002

Chronic inflammation and cancer.

A substantial body of evidence supports the conclusion that chronic inflammation can predispose an individual to cancer, as demonstrated by the association between chronic inflammatory bowel diseases and the increased risk of colon carcinoma. Chronic inflammation is caused by a variety of factors, including bacterial, viral, and parasitic infections, chemical irritants, and nondigestible particles. The longer the inflammation persists, the higher the risk of associated carcinogenesis. This review describes some of the underlying causes of the association between chronic inflammation and cancer. Inflammatory mediators contribute to neoplasia by inducing proneoplastic mutations, adaptive responses, resistance to apoptosis, and environmental changes such as stimulation of angiogenesis. All these changes confer a survival advantage to a susceptible cell. In this article, we discuss the contribution of reactive oxygen and nitrogen intermediates, prostaglandins, and inflammatory cytokines to carcinogenesis. A thorough understanding of the molecular basis of inflammation-associated neoplasia and progression can lead to novel approaches to the prevention and treatment of cancer.

Animals↗

PubMed2004

A primer on inflammation.

Inflammation is the localized, protective response of the body to injury or infection. The classic clinical signs that characterize inflammation are heat, redness, swelling, pain, and loss of function. During inflammation, cells and their secreted chemicals attempt to destroy, dilute, or wall off the injurious agent. A series of biochemical events cause the blood vessels to dilate and become more permeable, resulting in the activation of the complement, clotting, and kinin systems. The end result of inflammation is the return of function by the regeneration or repair of the affected tissue. In some instances, inflammation may continue for a prolonged period of time, producing untoward consequences for localized tissue as well as the entire body. The purpose of this article is to provide a basic and simplified understanding of how the inflammatory process functions in the human body.

Blood Coagulation↗

PubMed2000

Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies.

BACKGROUND: There have been no previous studies on the role of inflammation in the brain for the second most common dementing disorder, dementia with Lewy bodies. OBJECTIVE: To investigate the degree of cortical inflammation in dementia with Lewy bodies (DLB) compared with Alzheimer disease (AD) and control brains. DESIGN AND MAIN OUTCOME MEASURES: Post-mortem tissue collection from a brain donor program using standardized diagnostic criteria. Brains collected from January 1, 1993, through December 31, 1996, were screened and selected only for the presence or absence of tau neuritic plaques. Results of immunohistochemistry for HLA-DR were quantified using area fraction counts. Counts were performed by investigators who were unaware of the diagnosis. Results were compared across groups using analysis of variance and posthoc testing. SETTING: A medical research institute in Sydney, Australia. PATIENTS: Eight brains with DLB and without the tau neuritic plaques typical of AD, 10 brains with AD and no Lewy bodies, and 11 nondemented controls without significant neuropathological features were selected from a consecutive sample. RESULTS: Compared with AD, DLB demonstrated significantly less inflammation in the form of HLA-DR-reactive microglia in all cortical regions (P<.001, posthoc). The level of inflammation in DLB was comparable to that seen in controls (P=.54, post hoc). CONCLUSIONS: Inflammation appears related to the tau neuritic plaques of AD. Despite similar clinical presentations, therapeutic anti-inflammatory strategies are not likely to be effective for pure DLB. Arch Neurol. 2000.

Aged↗