How Chronic Latent Inflammation Is Measured

Article by SoLongevity Research

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Measuring chronic latent inflammation is not as simple as measuring acute inflammation associated with infection or disease. There are different types of tests and markers, with different sensitivities. Here is a brief guide to get your bearings

What this article is about

There are several ways to know whether our body is in a state of chronic latent (also called low-grade) inflammation.
Not all markers used in the various tests are equally valid and indicative. Therefore, there are different types of diagnostics for latent inflammation. The most accessible test is for high-sensitivity C Reactive Protein.

How is inflammation measured?

As we explained to you in a previous article, latent (or low-grade) inflammation is silent and very sneaky because it sets the stage for all aging-related diseases. But is it possible to detect and measure it? Yes, and there are several ways to do so. However, it is important to remember that the biomarkers used are not all sensitive and reliable in the same way.

First of all, it should be said that the classic tests used to detect acute inflammation are not used to pick up chronic inflammation. Take the case of ESR (erythrocyte sedimentation rate), for example. This index, which appears in blood tests, indicates the rate at which the corpuscular part of the blood sample (made incoagulable) settles at the base of the tube. This index increases in the presence of infectious and inflammatory diseases (such as rheumatoid arthritis) and beyond (heart attack, anemia, tumors…). When the ESR changes, however, it means that damage to the body is already present and is usually of great magnitude. The goal of measuring chronic latent inflammation, on the other hand, is to then be able to take action to prevent such damage from occurring.

Is it necessary to measure C-reactive protein (PCR)?

One parameter we often hear about is C-reactive protein (CRP). What is it? Let’s start by saying that it is a protein produced by the liver in high amounts when inflammation is ongoing, and it can be detected with a simple peripheral blood test (usually PCR reference values are less than 5-10 mg/L). Like the ESR, however, the normal PCR test also indicates damage that has already occurred and detects acute inflammation, whereas it is insensitive for latent chronic inflammation. The test for high-sensitivity C-reactive protein begins to be more indicative. In cardiology, for example, it is used to assess the risk of cardiovascular events, also related to atherosclerosis.

The goal of measuring chronic inflammation is to be able to take action to prevent associated diseases and improve health status

What is the purpose of measuring Interleukin-6?

In order to have more accurate and reliable measurements, we need to switch to another, more sophisticated type of diagnostic. One way is to detect some specific pro-inflammatory cytokinesCytokines are small proteins produced by the immune system, which bind to specific receptors present on the cell membrane and communicate to the cell a specific set of instructions such as, for example, the stimulus to grow, or to differentiate or even the order to die. They are produced by different types of cells and, once released in the body, induce specific reactions in adjacent cells (paracrine effect), in others far away (endocrine effect) or in those that have created them (autocrine effect). in the blood, such as IL-6 (interleukin-6), the most commonly cited by the scientific community. IL-6 is produced by cells of the immune system and is a marker of its activation because it increases in the presence of inflammation. Again, its levels are often associated with disease (autoimmune, cardiovascular, cancer) and it is often measured in patients with diabetes and other cardiovascular risk factors. Less used in clinical practice is the measurement of Neopterin. This molecule is also released by cells of the immune system (the macrophages) and indicates a pro-inflammatory immune state.

Several markers, including IL-6, allow assessment of the inflammatory state.

In addition to IL6, plasma levels of other inflammatory cytokines, such as TNF and IL1-beta, can be measured. However, since these are rather expensive measurements, they do not find frequent use in clinical practice. Also to be considered is the recent introduction of tests that measure salivary levels of these cytokines, for which, however, data are still lacking from clinical studies on large case series.

From a purely practical point of view, the most accessible marker to date remains the high-sensitivity PCR test, which tells us whether or not an inflammatory state is present

What other markers for low-grade inflammation?

From here we go up one more level of diagnostics. One of the markers that has recently emerged from the study of the genetics of aging is CXCL9, a cytokine that can assess the risk of cardiovascular disease (we discussed it in this article). It is a very important marker but very little used in clinical practice. In large studies of centenarians and healthy aging individuals, it has been shown that there are polymorphisms (i.e., variants that change by a single letter) of the gene encoding for CXCL9 that are associated with longevity, to the point that it is considered among the most important inflammatory markers in research. Staying on the topic of genetics and polymorphisms, it is possible to study those encoding, for example, for the aforementioned Interleukin 6 for Interleukin 10, TNF and IL1beta.

A final level of analysis for low-grade inflammation is what we are working on at SoLongevity. It is based on epigenetic modifications of some of our genes. It is in fact possible to measure the methylation level of inflammation-related genes.

What is the method conceived by SoLongevity?

From a purely practical point of view, the most accessible marker to date remains the high-sensitivity PCR test, which tells us whether or not an inflammatory state is present. But there is a final level of analysis for low-grade inflammation, which is what we are working on at SoLongevity, and that is based on epigenetic modifications of some of our genes. Indeed, it is possible to measure the level of methylation (the most important epigenetic modification) of genes related to inflammation, such as i-NOS (Inducible Nitric Oxide Synthase), a gene that is methylated or demethylated depending on inflammatory risk.

Such improvements can be achieved, for example, with specific nutritional supplements such as Cell-Fasting, or with anti-inflammatory drugs such as aspirin, or with actions on the gut microbiome and targeted dietary interventions. To measure the effectiveness of these interventions, C Reactive Protein is not enough: having tests and new biomarkers that we are working on, on the other hand, allows us to obtain very timely and useful information to improve our health.