Other Inflammatory Markers, Interleukin-6 (IL-6) and Cardiovascular Disease
Atherosclerosis and inflammation share similar basic mechanisms involving the adhesion of leukocytes to vascular endothelium in their early phases. There is a strong association between systemic inflammation and coronary artery disease. This association is thought to be causal, i.e. inflammation increases the risk of the disease, rather than simply marking the presence of atherosclerosis, which is an inflammatory process [56,57].
The relationship between infection and cardiovascular disease is likely to have several mediators (including possibly an autoimmune response against protein on the arterial endothelial cell wall) [58]. Cigarette smoking is a well established cardiovascular disease risk factor [59,64], as is high body mass index (BMI) [60], both providing a link between increased inflammation and increased risk. Although regular exercise reduces the risk of cardiovascular events, severe exercise has been shown to be associated with a systemic inflammatory response [65] and increased risk of myocardial infarction [66,67]. In contrast to the risks of severe exercise, moderate exercise and physical fitness are associated with lower baseline levels of inflammatory mediators [62,65,68,70].
Inflammatory markers such as C-reactive protein and fibrinogen are raised in affected people in both chronic coronary artery disease [60,62,63] and peripheral vascular disease compared with unaffected people [71]. The degree of inflammation correlates with disease severity [71,73].
Interleukin-6 (IL-6) is produced and released into the systemic circulation from subcutaneous adipose tissue as well as from cells of the immune system [74](Table 2). The levels correlate with BMI and percent body fat. A recent theory is that increased IL-6 may be the link between obesity and insulin resistance [75]. Adipose tissue secretes IL-6 whose levels and those of C-reactive protein also correlate with obesity and insulin resistance.
There is strong evidence supporting the central role of IL-6 in the inflammatory response. IL-6 is a 26 kDa cytokine, produced by many different cells in the body, including lymphocytes, monocytes, fibroblasts and endothelial cells. Various cytokines are involved in acute phase protein synthesis, including TNF
and IL-1. However, IL-6 is the only cytokine that can stimulate the synthesis of all the acute phase proteins involved in the inflammatory response: C-reactive protein, serum amyloid A, fibrinogen, 1-chymotrypsin and haptoglobin [76].
There is evidence that phospholipase A2 and cyclooxygenase pathways of AA metabolism are involved in the action of IL-6 in platelets (aggregation). Khalfoun et al. [77] examined the effects of PUFA on the production of IL-6 by human unstimulated endothelial cells and stimulated endothelial cells with TNF, IL-4, LPS (lipopolysaccharide) or PBL (allogeneic peripheral blood lymphocytes). The addition of EPA and DHA significantly reduced the production of IL-6 whereas AA was ineffective even at highest concentrations. EPA was more potent than DHA.
Interleukin-6 occupies a central place in the inflammatory response. Woods et al. [39] suggest a link between IL-6 and cardiovascular disease and the pathways involved (Fig. 2). The discovery of genetic polymorphisms involving a change of a single base, from guanine to cytosine, at position174 in the 5′ flanking region of the interleukin-6 gene is of great importance because the G allele is associated with higher IL-6 production than the C allele.
It is quite possible that genetic variation could account for the different responses to omega-3 fatty acids, both in terms of suppression of IL-6 and the inflammatory response [78]. In vivo studies found basal IL-6 levels to be twice as high in volunteers with the GG allele than in those with the CC allele.
Therefore, the understanding of the genetic mechanisms controlling the IL-6 levels as well as knowing the frequency of GG alleles in the population would provide further evidence that the higher levels of inflammation seen in patients with cardiovascular disease are primary rather than secondary in the development of cardiovascular disease.
Categories: Cardiovascular, Featured 3, Science, Treating Inflammation
Tags: atherosclerosis, BMI, C-Reactive Protein, Cardiovascular, CRP, DHA, EPA, inflammation, interlukin 6, TNF, tumor necrosis factor
Comments
Leave a Reply