Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

Abstract

Objective-To determine whether serum concentrations of the cytokines tumour necrosis factor a (TNFa) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. Design--A population based cross sectional study. Subjects and methods-198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. Results-Serum TNFa concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNFa was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNFa, each by approximately 50% (P < 0*05 for TNFa, P < 0 1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNFa and 36% for IL-6 (P = 0*14 for TNFa and P < 0*05 for IL-6). Conclusions-This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism. (Heart 1997;78:273-277) Keywords: C reactive protein; interleukin 6; TNFa; cardiovascular risk; coronary heart disease Cardiovascular risk factors as established in prospective studies could be considered to fall into two broad groups: endogenous and exogenous (lifestyle) Inflammation may be this mechanism.Most cardiovascular risk factors are changed in an adverse direction by acute inflammation: fibrinogen and the white blood cell count rise, glucose rises, HDL falls, and triglycerides rise.5-7 We have shown recently that low levels of systemic inflammation, as measured by serum C reactive protein in normal subjects, are related to many of these endogenous risk factors and that these levels of inflammatory activity are influenced in turn by many of the exogenous (lifestyle) cardiovascular risk factors.8 C reactive protein production by the liver is regulated by cytokines, principally interleukin 6 (IL-6), and tumour necrosis factor a (TNFa), which is the main trigger for the production of IL-6 by a variety of cells.9 The effect of these cytokines is modulated by cortisol and growth factors such as insulin.'0 In vitro and animal challenge experiments suggest that IL-6 and TNFa play important roles in the regulation of the synthesis of other acute phase proteins which are established risk factors for atherosclerosis, such as fibrinogen and factor VIII.10 These cytokines also have profound effects on lipid meta...

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

“…Previous studies have reported conflicting results about the relationship between IL-6 and HBP. 3,5,9,10,12,13,21,22 With one exception, 10 these studies were not designed to test the association between IL-6 and HBP, and failed to control for other cardiovascular risk factors. In fact, our results are consistent with those from the study of Chae et al, 10 the only other study in which appropriate control of confounding factors has been conducted.…”

“…31,32 Some reports of studies in human subjects have shown a significant association between TNF-a and elevated BP, 11,12,21 but others have failed to show such an association. 13,14 Unfortunately, none of these studies has been designed to test this hypothesis and all have failed to control for other risk factors. However, in experimental studies the degree of activation of the TNF-a system has been positively and significantly associated with systolic and diastolic BP.…”

“…9,10 Similarly, some studies in human subjects have shown a positive association between tumour necrosis factor alpha (TNF-a) level and HBP, 11,12 but others have not. 13,14 However, most of these studies were not designed to test the association between inflammation markers and HBP and have failed to control for other risk factors for HBP and for other inflammatory markers. Since Creactive protein (CRP) production by hepatocytes is regulated by cytokines, mostly IL-6 and TNF-a, 15 it is unlikely that any one inflammatory marker will fully reflect the complexity of mild chronic inflammation and capture its relationship with HBP.…”

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?

“…Previous reports have shown that the concentrations of TNF-␣ and other proinflammatory cytokines in peripheral blood are low. 48,49 Measurements are highly dependent on the sensitivity of the assays used, and some samples may fall below the limit of detection, mainly in healthy controls, as observed in our individuals.…”

Elevated C-Reactive Protein

“…These results are consistent with the role of human AT in the regulation of CRP levels. 11,12,14,34 In a random sample of 303 men aged 50 to 69 years, Mendall et al 34 had reported a significant association between the BMI and CRP levels. A significant relationship of CRP levels with the BMI was also noted among elderly men and women in the Cardiovascular Health Study.…”