Raised Inflammatory Markers Somewhat Correlate with Incidence of Age-Related Disease
Onset, progression, and resolution of inflammation are all driven by the interaction of many different complex signaling processes. The immune system as a whole is highly complex, an array of many different interacting populations of specialized cells. Nonetheless, there are a few individual circulating signal proteins that, to some degree at least, tend to reflect overall inflammatory status. Not reliably, but enough to produce correlations in patient populations of any reasonable size.
Today's open access paper is a survey of the literature on inflammatory cytokines IL-6, TNF, and IL-1β, pulling reported measures and patient comorbidities from many different published studies. As one might expect, there is a correlation between raised levels of inflammatory cytokines and the presence of age-related disease. Chronic inflammation is a feature of aging, and it is known to accelerate the progression of all of the common age-related conditions. The correlation isn't large or strong, however, indicating the point made above: individual cytokines are not great measures of the state of the immune system, and what they do in fact reflect varies widely from individual to individual. The state of chronic, unresolved inflammation is too complex to be measured so simply.
Level of IL-6, TNF, and IL-1β and age-related diseases: a systematic review and meta-analysis
Aging facilitates a pro-inflammatory state by disrupting the peripheral immune system, which leads to excessive innate immune activity with the release of pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Different pro-inflammatory cytokines, such as interleukins: IL-1β, IL-6, IL-12, IL-18, interferon (IFN-γ), and tumor necrosis factor (TNF), as well as anti-inflammatory ones, such as IL-4, IL-10, IL-13, and IL-19 which are secreted from immune cells, interact with body cells to mediate the immune responses and thus elicit its most optimum outcome.
Elevated levels of interleukin-6 and TNF, as well as IL-1β, are associated with diseases, disability, and mortality in older adults. Interleukin-6, also known as 'the cytokine for gerontologists', plays a key role in the acute phase response in metabolic control and in the pathogenesis of many chronic diseases. IL-6 is produced mainly by the monocytes and macrophages. It produces a pleiotropic effect, and although in healthy and younger people its level is usually relatively low, in the elderly its elevated levels may correlate with increased mortality. IL-1β is produced in large quantities during infections and other stressful events. High glucose concentration was reported to stimulate the production of IL-1β by pancreatic β cells, which implies the role of this cytokine also in type 2 diabetes. TNF is a pro-inflammatory mediator that can produce beneficial effects when activated locally in the tissues but it can be highly harmful when released systemically. It is one of the most important cytokines, produced by several types of cells: monocytes, T-cells, macrophages, fibroblast, adipocytes, and smooth muscle cells. In elderly people and centenarians, it has been shown that the level of TNF rises, which significantly increases mortality.
The assessment of chronic inflammation, including the level of pro-inflammatory cytokines in elderly people with comorbidities, may be the key to more effective treatment. Our hypothesis was that independent measurements of cytokines such as IL-6, TNF and IL-1β were significantly associated with the development of age-related diseases. Therefore, the aim of this study was to independently evaluate three cytokines: IL-6, TNF and IL-1β in elderly people with comorbidities compared to disease-free controls.
The electronic bibliographic PubMed database was systematically searched to select all the relevant studies published up to July 2023. The total number of the subjects involved in the meta-analysis included patients with diseases (n = 8,154) and controls (n = 33,967). The overall concentration of IL-6 was found to be higher in patients with diseases compared to controls and the difference was statistically significant. The heterogeneity was considerable. The potential diagnostic usefulness of IL-6 was confirmed by odds ratio (OR) analysis, with OR = 1.03. The concentration of both TNF and IL-1β was elevated in the control group compared to patients. For TNF, however, the difference was statistically insignificant.