Risk Of Chronic Inflammatory Diseases Research Articles

Healthy lifestyles ameliorate an increased risk of periodontitis associated with polycyclic aromatic hydrocarbons

The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001–2004 and 2009–2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH–periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.

Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016-2018.

Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests. Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

Vitamin D, the Sunshine Molecule That Makes Us Strong: What Does Its Current Global Deficiency Imply?

Vitamin D3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D3 are yet to be considered, and the function of vitamin D2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy.

Risk factors and sequelae of epidermolysis bullosa acquisita: A propensity-matched global study in 1,344 patients.

Identification of risk factors and sequelae of any given disease is of key importance. For common diseases, primary prevention and disease management are based on this knowledge. For orphan diseases, identification of risk factors and sequelae has been challenging. With the advent of large databases, e.g., TriNetX, this can now be addressed. We used TriNetX to identify risk factors and sequelae of epidermolysis bullosa acquisita (EBA), a severe and orphan autoimmune disease. To date, there is only enigmatic information on EBA comorbidity. We recruited 1,344 EBA patients in the Global Collaborative Network of TriNetX. Using the "explore outcomes" function we identified 55 diagnoses with a different prevalence between EBA and no-EBA patients. We next performed propensity-matched, retrospective cohort studies in which we determined the risk of EBA development following any of the identified 55 diseases. Here, 31/55 diseases were identified as risk factors for subsequent EBA. Importantly, the highest risk for EBA were other chronic inflammatory diseases (CID), especially lupus erythematosus and lichen planus. Lastly, we determined the risk to develop any of the identified diseases after EBA diagnosis. Here, 38/55 diseases were identified as sequelae. Notably, EBA patients showed an increased risk for metabolic and cardiovascular disease, and thrombosis. Furthermore, the risk for CIDs, especially lupus erythematosus and lichen planus, was elevated. These insights into risk factors and sequelae of EBA are not only of clinical relevance, e.g., optimizing cardiovascular disease risk, but in addition, point to shared pathogenetic pathways between EBA and other inflammatory diseases.

Knowledge, risk perceptions and practices surrounding chronic inflammatory diseases among first and second generation South Asian immigrants parents and children

PurposeThe purpose of this study is to examine knowledge and perceptions of risk surrounding chronic inflammatory diseases (CIDs) and intergenerational development, as well as practices used to acquire CID information among unaffected first- and second-generation South Asian immigrant parents and children in the Greater Toronto Area, Ontario.Design/methodology/approachFifty-four in-depth interviews with parents and children (18 parents, 36 children) were conducted by trained facilitators, recorded, transcribed and analyzed qualitatively.FindingsFindings reveal that although CIDs disproportionately affect South Asian immigrants, this group has low knowledge and awareness of CID symptoms, risk factors and conditions. Yet when equipped with some knowledge about CIDs, participants linked their increased risk of CIDs to perceived risks in their broader environments such as climate variations, pollution, unhealthy food environments and health system neglect, that although yearning to change these factors, felt unable to modify their risks as factors were beyond their control. Although information is critical to manage CIDs, the findings reveal important and divergent knowledge pathways and practices used among first- and second-generation parents and children, particularly related to health-care settings and academic resources, underscoring generational disparities in knowledge acquisition.Originality/valueThe findings suggest that a multi-sector, multi-tiered approach built around a series of structural interventions, programs and policy changes is needed to address CID knowledge and awareness gaps and entrenched culturally insensitive health care to create more equitable access to healthy, safe and responsive environments and care systems for CID management.

Вплив екзогенних факторів на геномний імпринтинг . 1. Вплив дієти і забезпеченості мікронутрієнтами матері на геномний імпринтинг нащадків

У статті проведено аналіз впливу раціону матері під час вагітності на становлення геномного імпринтингу плода. Показано, що зміни метилювання ДНК імпринтованих генів, індуковані порушенням забезпечення протеїнами і мікронутрієнтами, супроводжуються відхиленнями фізичного розвитку і підвищеним ризиком розвитку хронічних запальних захворювань, хвороб серцево-судинної системи, метаболічного синдрому в дитини в постнатальному періоді життя. Підкреслюється, що для запобігання розвитку імпринтинг-асоційованої патології у дитини при формуванні раціону вагітних жінок особлива увага повин­на бути приділена достатності вмісту в їх дієті протеїнів, фолієвої кислоти, метіоніну й вітамінів групи B.

Chronic radiation exposure aggravates atherosclerosis by stimulating neutrophil infiltration

Background Radiation exposure is known to increase the risk of chronic inflammatory diseases, such as atherosclerosis, by modulating inflammation. Methods To investigate the infiltration of leukocytes in radiation-aggravated atherosclerosis, we examined low-density lipoprotein receptor-deficient (Ldlr–/–) mice and C57BL/6j mice after exposure to 0.5 or 1 Gy radiation over 16 weeks. Results We found that radiation exposure induced atherosclerosis development in Ldlr–/– mice, as demonstrated by increased lipid-laden plaque size, reactive oxygen species levels, and levels of the pro-inflammatory cytokines, IL-1β and TNF-α, in the aortas and spleens. Total plasma cholesterol, triglyceride, and LDL cholesterol levels were also increased by radiation exposure, along with cardiovascular risk. We also showed dose-dependent increases in neutrophils and monocytes that coincided with a reduction in lymphocytes in the spleens of Ldlr–/– mice. The correlation between the infiltration of leukocytes and cytokine production was also confirmed in the hearts and spleens of these mice. Conclusions We concluded that chronic radiation exposure increased the production of pro-inflammatory mediators, which was associated with the migration of neutrophils and inflammatory monocytes into sites of atherosclerosis. Thus, our data suggest that the accumulation of neutrophils and inflammatory monocytes, together with the reduction of lymphocytes, contribute to aggravated atherosclerosis in Ldlr–/– mice under prolonged exposure to radiation.

Caesarean Delivery and Risk of Chronic Inflammatory Diseases (Inflammatory Bowel Disease, Rheumatoid Arthritis, Coeliac Disease, and Diabetes Mellitus): A Population Based Registry Study of 2,699,479 Births in Denmark During 1973-2016.

BackgroundChronic inflammatory diseases in childhood and early adult life share aetiological factors operating from birth and onwards. In this study, we use data from the national Danish health registers to evaluate the risk of developing four common, immune-mediated hospital-diagnosed childhood chronic inflammatory diseases.MethodsA national population-based registry study. Data from the Danish Medical Birth Registry and the Danish National Patient Registry from January 1973 to March 2016 were linked at a personal level to evaluate any potential associations between caesarean section and development of Inflammatory bowel diseases, rheumatoid arthritis, coeliac disease and diabetes mellitus among the offspring. A model adjusted for parental age at birth, decade of birth, gender of child, and parents’ chronic inflammatory disease status was used. ResultsThis register-based national cohort study of 2672708 children with information on delivery mode found an increased risk of diabetes, arthritis, coeliac disease, and inflammatory bowel disease for both girls and boys after caesarean section compared with vaginal delivery. The higher risk was present at least 40 years after delivery. In a subgroup analysis, both acute and elective caesarean section was associated with an increased risk of developing a chronic inflammatory disease.ConclusionsBeing born by caesarean section leads to increased host susceptibility for chronic inflammatory diseases that last for decades. This finding should be further addressed in future studies with the aim to support the development of new strategies for prevention, treatment, and maybe even cure.

Development of a beverage based on citric juice with the addition of whey

Abstract Faced with new trends in healthy eating, there is a need to expand this market. The Argentine Society of Nutrition, based on local and international studies, has suggested that an adequate intake of dairy products not only provides calcium but also provides compounds associated with a decrease in the risk of chronic inflammatory diseases. The objectives of this work were to formulate and develop beverages based on orange juice with the addition of liquid and powdered whey, sweetened naturally, and study the physicochemical, nutritional and sensory characteristics. The samples were homogenized and pasteurized at 85 °C for 30 minutes and the pH value, acidity, solids content and colour were analyzed. A just-about-right (JAR) scale was used to evaluate the intensities of the acid taste, bitter taste and flavour, and also the colour attributes, and a 5-point hedonic scale was used to evaluate the global acceptability of the samples. The intensity analyses showed that the taste and colour were “ideal”. With respect to global acceptability, the pleasant categories scored more than 60% and only 10% considered it unpleasant. The beverage presented a pH value, colour and solids content similar to those of other citrus beverages, and was rated as pleasant by the consumers.

Dietary cranberry suppressed colonic inflammation and alleviated gut microbiota dysbiosis in dextran sodium sulfate-treated mice.

Increased consumption of fruits may decrease the risk of chronic inflammatory diseases including inflammatory bowel disease (IBD). Gut microbiota dysbiosis plays an important etiological role in IBD. However, the mechanisms of action underlying the anti-inflammatory effects of dietary cranberry (Vaccinium macrocarpon) in the colon and its role on gut microbiota were unclear. In this study, we determined the anti-inflammatory efficacy of whole cranberry in a mouse model of dextran sodium sulfate (DSS)-induced colitis, as well as its effects on the structure of gut microbiota. The results showed that dietary cranberry significantly decreased the severity of colitis in DSS-treated mice, evidenced by increased colon length, and decreased disease activity and histologic score of colitis in DSS-treated mice compared to the positive control group (p < 0.05). Moreover, the colonic levels of pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) were significantly reduced by cranberry supplementation (p < 0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels revealed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice. α diversity was significantly decreased in the DSS group, compared to the healthy control group. But, cranberry treatment significantly improved DSS-induced decline in α-diversity. Moreover, cranberry treatment partially reversed the change of gut microbiota in colitic mice by increasing the abundance of potential beneficial bacteria, for example, Lactobacillus and Bifidobacterium, and decreasing the abundance of potential harmful bacteria, such as Sutterella and Bilophila. Overall, our results for the first time demonstrated that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of colitis in DSS-treated mice.

Sex-specific association between prenatal life stress exposure and infant pro-inflammatory cytokine levels during acute respiratory infection

BackgroundPrenatal life stress exposure is linked to dysregulated immune function and chronic inflammatory disease in offspring, but we know little about its effects on infant immune response during viral infection. MethodTo address this issue, we examined associations between prenatal life stress exposure and infant upper-airway inflammatory markers during acute respiratory infection (ARI) using data from a prospective, population-based birth-cohort study (N = 180). Infant inflammation was measured as a continuous latent factor within a structural equation modeling framework using nasal wash concentrations of interleukin-1β, interleukin-6, and tumor necrosis factor-α. We hypothesized that infants exposed to prenatal life stress would have greater levels of nasal inflammation during ARI and increased risk for ARI-related morbidity in early childhood. ResultsOur findings contradicted these hypotheses and provided evidence of sexually dimorphic effects of prenatal stress exposure on infant immune functioning during ARI. Among boys, but not girls, prenatal stress was negatively associated with nasal inflammation and indirectly associated with both lower ARI severity and reduced likelihood of subsequent ARI-related hospitalization in the 2nd and 3rd years of life. ConclusionThese data suggest that prenatal stress exposure may be beneficial for infant boys in the context of respiratory viral infections; however, it will be critical to determine if these benefits are offset by increased risk for chronic inflammatory diseases in later childhood. As the participants in this cohort are being followed longitudinally through age 8, we will be able to evaluate long-term health outcomes in future studies.

Whole Blood Transcriptional Profiling Reveals Highly Deregulated Atherosclerosis Genes in Myeloproliferative Cancer

Introduction: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPNs but also potentially having an impact upon the development of accelerated (premature) atherosclerosis, which is recorded in several other inflammatory diseases. Using whole blood gene expression profiling we have previously reported massive deregulation of inflammation genes and genes involved in oxidative stress. Herein, we extend our studies to explore the landscape of atherosclerosis genes, which have not been investigated previously in MPNs but may add novel important information in regard to deregulation of these genes of potential importance for the development of premature atherosclerosis and accordingly the heavy cardiovascular disease burden in MPNs.Methods:Global gene expression profiling was performed on 21 control subjects, 19 patients with ET, 41 patients with PV, and 9 patients with PMF. Gene expression profiles were generated using Affymetrix HG-U133 2.0 Plus microarrays recognizing 54.675 probe sets (38.500 genes). Total RNA was purified from whole blood, amplified to biotin-labeled aRNA, and hybridized to microarray chips. The R statistical software was applied to perform data preprocessing and statistical analysis of microarray data.Results:We identified 20,439, 25,307, and 17,417 probe sets that were differentially expressed between controls and patients with ET, PV, and PMF, respectively (FDR£0.05). These genes included 84 genes represented on the Qiagen Human Atherosclerosis gene panel. In patients with ET, FABP3, FN1, LIF, LPL, PDGFB, PDGFRB, PPARD, SERPINE1, and TGFB2 were among the 28 upregulated genes, and APOE, BCL2, ITGA5, KLF2, NFKB1, and SELPLG were among the 17 downregulated genes. In patients with PV, 39 atherosclerosis genes were upregulated including VCAM1, FN1, PDGFRB, LPL, TGFB2, SERPINE1, PDGFB, and LIF, and 17 genes were downregulated including APOE, ITGA5, KLF2, NFKB1, SELPLG, and BCL2. In patients with PMF, PDGFB, HBEGF, LIF, PDGFRB, SERPINE1, TGFB2, and VWF were among the 24 upregulated genes, and KLF2, BCL2, IL1R2, NFKB1, ITGB2, ITGA5, IFNAR2, and SELPLG were among the 22 downregulated genes. BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated, whereas BCL2 were progressively significantly downregulated from ET over PV to PMF (all FDR<0.05). The top 15 significantly up- and downregulated genes are shown in Table 1 and 2, respectively.Discussion and conclusions: Atherosclerosis is a chronic inflammatory disease, which involves several circulating blood cells, including both leukocytes and platelets. Taking into account that chronic inflammation today is considered of utmost importance in MPN-pathogenesis and MPNs carry an increased risk of chronic inflammatory diseases, such as inflammatory bowel diseases, age related macular degeneration and chronic kidney diseases, which all are associated with early development of atherosclerosis, we speculated if whole blood gene expression profiling of all the inflammatory cells (granulocytes, monocytes, platelets etc) being involved in the atherosclerotic process might unravel deregulation of atherosclerosis genes and perhaps depict a particular MPN-atherosclerosis gene signature. Indeed, in the present study we have found that several genes of importance for the development of atherosclerosis are highly deregulated and a subset of 6 genes (BCL2L1, MMP1, PDGFA, PTGS1, and THBS4) were progressively significantly upregulated, in the biological “ inflammatory ” continuum from the early cancer stages (ET/PV) to the advanced myelofibrosis stage, whereas BCL2 was progressively and significantly downregulated. In conclusion, we have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of the cell types (leukocytes, platelets, endothelial cells) being deeply involved in the atherosclerotic process. The significance of our observations should be further explored and confirmed in other MPN-cohorts and the impact of cytoreductive therapy (e.g interferon-alpha2) and statins upon deregulated genes as well. [Display omitted] DisclosuresHasselbalch:Novartis: Research Funding.

Smokers Display Reduced Glucocorticoid Sensitivity Prior to Symptomatic Chronic Disease Development.

Chronic stress plays a critical role in many of today's diseases and causes of death. Tobacco use reliably increases the likelihood of chronic disease development and premature death. In addition, habitual tobacco use elevates risk of chronic inflammatory diseases, and glucocorticoid therapy is often less effective in smokers compared with nonsmokers. Taken together, smokers may develop glucocorticoid insensitivity, thereby removing the body's greatest anti-inflammatory mechanism. The purpose of this study was to examine glucocorticoid sensitivity among 24 smokers and 24 age-, sex-, and body mass index-matched never smokers who were clinically healthy individuals (i.e., no diagnosis or medication use for chronic diseases and normotensive). Participants visited the lab after a 12 hr fast, provided a blood sample, and completed a series of psychosocial questionnaires. Smokers continued smoking ad libitum before the lab visit. Group differences in glucocorticoid sensitivity were examined using ANCOVA and repeated with linear mixed model to account for possible dependence among immune outcomes that matching participants on age, sex, and body mass index may have introduced. Prior to clinical disease onset, smokers' peripheral blood mononuclear cells (PBMCs) exhibited reduced glucocorticoid sensitivity as well as a diminished inflammatory response to lipopolysaccharide compared with never smokers' PBMCs; results were identical regardless of statistical modeling used. Cigarette smoking, a self-initiated pharmacological chronic stressor, may provide a unique opportunity to examine early wear and tear on physiological functioning that may lead to chronic disease development. Additional research into PBMCs' intracellular changes must be examined as well as repeating this study in a larger, more heterogeneous population.

Diet, Obesity, and Asthma.

Obesity has reached epidemic proportions in many developed countries as Western dietary patterns have been widely adopted. These diets are characterized by excess energy intake as well as regular consumption of processed or "fast" foods and limited consumption of fruit, vegetables, and whole grains. The result is a high intake of saturated fat, refined carbohydrates, and sodium; and a low intake of fiber, vitamins, and other phytochemicals. This type of poor-quality diet has been associated with increased risk of chronic inflammatory diseases, including asthma. Of particular note, high intake of saturated fat stimulates proinflammatory pathways via activation of pattern recognition receptors, endoplasmic reticulum stress, and fatty acid-binding protein activity. Conversely, with a low intake of soluble fiber, beneficial antiinflammatory mechanisms, such as free fatty acid receptor activation and histone deacetylase inhibition, are suppressed. Similarly, with a low intake of antioxidants such as vitamin C, vitamin E, and carotenoids, nuclear factor κ-light-chain-enhancer of activated B cells activity is enhanced, creating a proinflammatory environment. There is evidence derived from human and experimental models of asthma suggesting that these mechanisms contribute to the development of airway inflammation, loss of asthma control, and/or worse lung function. Obese individuals have increased asthma morbidity and reduced quality of life, so strategies for better management of these patients are urgently needed. Evidence suggests that, in addition to reducing the quantity of food consumed, interventions should also target the quality of food consumed to improve both asthma management and the overall health and well being of these patients.

Allergy - an environmental disease

The increase in allergies is aphenomenon that is being observed in all fast-developing countries. For along time, science has taken as astarting point that solely agenetic predisposition is aprecondition for the development of an allergy. Today, knowledge of environmental factors that can alter genes or the transcription of genes in the cells, has improved. Epidemiological studies have meanwhile identified several environmental factors that have aprotective or supporting effect on allergy development. The environmental microbiome has recently gained central interest. Acommon theme in most of the studies is diversity: reduced diversity is correlated with enhanced risk for chronic inflammatory diseases and allergy.It is now of great interest for research to further analyze such environment-gene and/or environment-human interactions on all levels - from organs to cells to small and microstructures such as genes. For immunologists, it is specifically about understanding the influencing factors and effector pathways of allergens, and to apply thereby obtained insights in the follow-up for the ultimate goal of allergy research - prevention.

Gut microbiota-host interactions and juvenile idiopathic arthritis.

BackgroundJuvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease.Main bodyRecent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself.ConclusionsThe microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

Protection against chemotaxis in the anti-inflammatory effect of bioactives from tomato ketchup.

The consumption of tomato products has been associated with a decreased risk for chronic inflammatory diseases. In this study, the anti-inflammatory potential of tomato ketchup was evaluated by studying the effect of tomato ketchup extracts and bioactives from tomato ketchup on human monocytes and vascular endothelial cells (HUVEC). HUVEC were pre-treated for 1 h with either individual bioactives (7.5 µM lycopene, 1.4 µM α-tocopherol or 55 µM ascorbic acid) or a combination of these three compounds, or with the hydrophilic or lipophilic tomato ketchup extracts or with the two extracts combined. After the pretreatment, the cells were washed and challenged with TNF-α (10 ng/ml) for 6 h. The medium was used for the determination of the release of cytokines and the chemotaxis of monocytes. Inflammatory protein expression and production were assayed with real-time RT-PCR and ELISA. It was found that tomato ketchup extracts significantly reduced gene expression and release of the pro-inflammatory cytokines TNF-α and IL-8 in HUVEC after the inflammatory challenge, whereas the release of the anti-inflammatory cytokine IL-10 was increased. Chemotaxis was effectively impeded as demonstrated by a reduced monocyte migration. This effect correlated with the reduction of IL-8 production in the presence of the test compounds and extracts. The results consistently emphasize the contribution of lycopene to the anti-inflammatory effect of tomato ketchup. Other compounds in tomato ketchup such as α-tocopherol and ascorbic acid appeared to strengthen the anti-inflammatory effect of lycopene. The tomato ketchup extracts subtly interfered with several inflammatory phases that inhibit chemotaxis. Such a pleotropic mode of action exemplifies its potential mitigation of diseases characterized by prolonged low grade inflammation.

OP0087 Use of Moist Snuff and the Risk of Developing Rheumatoid Arthritis; Results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis Study

BackgroundSmoking is the major known environmental risk factor for RA, and notably this risk factor is exclusively seen in ACPA-positive RA. Whether this increased risk is due to nicotine or...

Early life environment and developmental immunotoxicity in inflammatory dysfunction and disease

Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory-mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation.

Smoking, Use of Moist Snuff, and Risk of Chronic Inflammatory Diseases

Cigarette smoking is emerging as a strong risk factor in the otherwise unknown etiology of chronic inflammatory diseases. Whether the same applies also to smokeless tobacco remains unknown. Nicotine is a powerful modifier of the inflammatory response. By comparing risks associated with tobacco smoking and with smokeless tobacco, the role of nicotine in the development of chronic inflammation may be evaluated. To assess and compare the risks of rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), sarcoidosis, and multiple sclerosis (MS) associated with cigarette smoking and with the use of Swedish moist snuff. We performed a cohort study of 277,777 males within a cohort of Swedish construction workers who had provided information about tobacco use in 1978-1993. Cross-linkage to the nationwide Swedish Hospital Discharge Register provided information about the occurrence of RA, UC, CD, sarcoidosis, and MS through 2004. Age-adjusted relative risks (RRs) associated with smoking and moist snuff, respectively, were estimated by Cox regression. Ever-smoking was associated with an increased risk for RA (RR, 2.1; 95% confidence interval [CI], 1.7-2.5), CD (RR, 1.5; 95% CI, 1.2-1.8), MS (RR, 1.9; 95% CI, 1.4-2.6), and UC (RR, 1.3; 95% CI, 1.1-1.5, confined to ex-smokers), and a decreased risk of sarcoidosis (RR, 0.5; 95% CI, 0.4-0.5). By contrast, ever-use of moist snuff, adjusted for smoking, was not associated with RA (RR, 1.0; 95% CI, 0.9-1.2), UC (RR, 1.1; 95% CI, 0.9-1.2), CD (RR, 0.9; 95% CI, 0.8-1.1), sarcoidosis (RR, 1.1; 95% CI, 0.8-1.5), or MS (RR, 1.0; 95% CI, 0.8-1.4). Smokeless tobacco does not increase the risk of chronic inflammatory diseases, suggesting that inhaled nonnicotinic components of cigarette smoke are more important than nicotine itself in the etiology of these diseases.