Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.

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Inflammatory responses and inflammation-associated diseases in organs

Coronary heart disease

Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction—both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension—such as activation of the sympathetic nervous system, aging, and elevated aldosterone—are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future.

https://downloads.hindawi.com/journals/bmri/2014/406960.pdf

Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension

Although there is a correlation between hypertension and levels of interleukin (IL) 6, the exact role this cytokine plays in myocardial remodeling is unknown. This is complicated by the variable tissue and circulating levels of IL-6 reported in numerous experimental models of hypertension. Accordingly, we explored the hypothesis that elevated levels of IL-6 mediate adverse myocardial remodeling. To this end, adult male Sprague-Dawley rats were infused with IL-6 (2.5 microg . kg(-1) . h(-1), IP) for 7 days via osmotic minipump and compared with vehicle-infused, aged-matched controls. Left ventricular function was evaluated using a blood-perfused isolated heart preparation. Myocardial interstitial collagen volume fraction and isolated cardiomyocyte size were also assessed. Isolated adult cardiac fibroblast experiments were performed to determine the importance of the soluble IL-6 receptor in mediating cardiac fibrosis. IL-6 infusions in vivo resulted in concentric left ventricular hypertrophy, increased ventricular stiffness, a marked increase in collagen volume fraction (6.2% versus 1.7%; P<0.001), and proportional increases in cardiomyocyte width and length, all independent of blood pressure. The soluble IL-6 receptor in combination with IL-6 was found to be essential to producing increased collagen concentration by isolated cardiac fibroblasts and also played a role in mediating a phenotypic conversion to myofibroblasts. These novel observations demonstrate that IL-6 induces a myocardial phenotype almost identical to that of the hypertensive heart, identifying IL-6 as potentially important in this remodeling process.

Interleukin 6 Mediates Myocardial Fibrosis, Concentric Hypertrophy, and Diastolic Dysfunction in Rats

Global association between ambient air pollution and blood pressure: A systematic review and meta-analysis

High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-alpha), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-alpha, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP >or=140 and/or diastolic BP >or=90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P=0.003), third (PR: 2.32; P=0.031), and fourth quartiles (PR: 2.30; P=0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-alpha levels were 1.41 (P=0.014) for the second; 1.59 (P=0.001) for the third; and 1.61 (P=0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-alpha and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension

The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be population-dependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n=256) and 257 age and sex group-matched controls from a random sample of free living Colombians (n=2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equilibrium in controls, with the exception of M235T, which showed a small excess of heterozygotes (p=0.005; disequilibrium coefficient, D=-0.0264). After adjustment for age, sex, body mass index, race, physical activity, family history of hypertension and cardiovascular disease, and other polymorphisms, subjects with the ACE DD genotype were 1.56 times (95% confidence interval [CI]: 1.05, 2.33) more likely to be hypertensive than carriers of the I allele (p=0.03). Also, adjusted systolic and diastolic blood pressure were 4.58 (95% CI: -0.39, 9.56) and 3.32 (95% CI: 0.78, 5.86) mmHg higher in DD homozygous individuals than in carriers of the I allele, respectively. Approximately 15% of the cases of hypertension in this population could be attributed to carriage of the DD genotype. None of the other polymorphisms was associated with either hypertension or blood pressure level. In conclusion, the ACE DD genotype appears to be an independent risk factor for development of hypertension and may explain a significant fraction of incident cases among Hispanics.

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Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics.

BACKGROUND: The ACE gene insertion/deletion polymorphism has been studied as a risk factor for acute myocardial infarction (AMI) in different populations with conflicting results. MATERIAL/METHODS: We conducted a case-control study in first AMI cases matched by age (+/-5 years) and sex to controls with non-cardiac diseases to ascertain whether Colombian carriers of the DD genotype were at higher risk of AMI than carriers of the ID and II genotypes. Zygosity for the deletion-insertion (D-I) of the ACE gene polymorphism was determined by polymerase chain reaction. Logistic regression with adjustment for matching factors was used to estimate the independent effect of the DD polymorphism after controlling for traditional cardiovascular risk factors. RESULTS: Participants (n=202) had a mean age of 62 years and 32% were women. The distribution of the polymorphism was significantly different (p=0.001) in cases (II 8.9%; ID 51.5%; DD 39.6%) and controls (II 8.9%; ID 64.4%; DD 26.7%). After adjustment for other risk factors, the risk of AMI in subjects with genotype DD was 1.98 times higher than the risk in the combined group of genotypes II and ID (95% CI: 1.01, 3.87; p=0.04). There was a significant DD by age interaction (p=0.002). In subjects p=0.86), while in subjects <60 years the risk increased 5.16 times (95% CI: 1.68, 15.90; p=0.004). CONCLUSIONS: These results support an increased risk of AMI in Colombian subjects <60 years with the ACE DD genotype.

Angiotensin-converting enzyme gene polymorphism and risk of myocardial infarction in Colombia.

Objective: to determine the association between blood group A and gastric cancer. Patients and methods: a study of cases and controls was performed; the patients had gastric cancer confirmed by histopathology, were taken care of in the oncology unit of the Hospital Universitario de Santander between january 2001 and december 2005, living in Bucaramanga and in the influence area of the institution; the controls were patients admitted in the hospital in the general internal medicine service due to medical causes different from gastric cancer and patients in the gastroenterology unit who were subject to upper gastrointestinal tract endoscopy with normal results. Those patients from whom there was no information or those that did not wish to participate were excluded. The data were taken from the clinical histories or by telephone if more details were needed. A data base was built on Microsoft Access 2003, and later on they were analyzed using the Stata 9.0 software. Results: 208 clinical histories of patients with cancer were reviewed of which 153 met the inclusion criteria and the information was complete. The prevalence of the different blood groups in the population studied was: 56.74% for group O, 32.17% for group A, 10.22% for group B and 0.87% for group AB. A statistically significant association was found between gastric cancer in blood group A showing an RO = 2.22 (IC 95%: 1.38-3.57); an association was found between gastric cancer and first consanguinity family members with a different type of cancer, RO =1.91 (CI 95%: 1.05-3.46). Besides the above, the logistic regression multivariable analysis showed that being less than 50 years old reduced the risk of cancer (RO = 0.44, CI 95%: 0.26-0.77). No association was found between eating habits such as fruits and vegetables, cereals, coffee, corn bread from Santander, processed meats, salty food and hot pepper with the onset of gastric cancer. The predominant cancer type was adenocarcinoma, intestinal variety with 45.75% and the anthral - pyloric location with 43.14%. The proportion of Helicobacter pylori reported by pathology was 30.07%.

Grupo sanguíneo A y riesgo de cáncer gástrico en el Hospital Universitario de Santander (Bucaramanga, Colombia)

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Germán Gamarra

Papers

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension

Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics.

Angiotensin-converting enzyme gene polymorphism and risk of myocardial infarction in Colombia.

Grupo sanguíneo A y riesgo de cáncer gástrico en el Hospital Universitario de Santander (Bucaramanga, Colombia)

Blood group A and gastric cancer risk in the Hospital Universitario de Santander (Bucaramanga, Colombia)