Chronic, Low-Grade Inflammation: Most Common Causes

Author:
Hussain Basheer

1. Obesity 2. Chronic Sleep Deprovision 3. Dormant Infections 4. Smoking/ Vaping 5. Psychological Stress Conclusion

Summary

● Excess adipose tissue promotes chronic inflammation, contributing to insulin resistance and metabolic disease.

● Poor sleep duration and quality increase inflammatory markers and cardiovascular disease risk.

● Dormant H. pylori can evade detection, reactivate, and contribute to gastric cancer.

● Vaping causes measurable inflammation and respiratory harm, though generally less than smoking.

● Chronic stress disrupts cortisol regulation, weakens immunity, and increases inflammatory activity.

Introduction

Inflammation is often described as the body’s repair signal, but when it becomes persistent, it can quietly contribute to disease.

Modern health risks such as obesity, poor sleep, chronic infections, smoking or vaping, and psychological stress appear very different on the surface, yet they share a common biological thread: chronic low-grade inflammation.

This article explores how these everyday exposures can disrupt metabolism, damage blood vessels, weaken immune regulation, and increase long-term disease risk.

By examining the evidence behind each factor, a clearer picture emerges of how lifestyle, environment, infection, and stress can gradually shape physical health.

1. Obesity

Obesity is a risk factor for both cardiovascular disease and type 2 diabetes mellitus, and one of the mechanisms which explains this association is chronic low-grade inflammation. <tt>2050</tt>

Most individuals with obesity are insulin resistant; this means the insulin receptors on the surface of cells across various organs have a diminished response to the necessary effects of insulin.

Since insulin acts as somewhat of a “gatekeeper”, it regulates the timing and quantity of molecules—most notably glucose—transported across the cell membrane, which can then be used to produce the energy currency ATP.

Chronic cytokine exposure is a leading explanation for insulin receptor dysfunction.

These cytokines are produced through the activation of pro-inflammatory genes and function as a signal for immune cells to repair adipocytes, e.g., in the case of obesity, which have become stressed and hypertrophied (swollen) from the excess intake of triglycerides due to overnutrition.

In fact, when human randomised control trials involve blocking the receptors these cytokines use to trigger intracellular inflammation, 'glycaemia [blood sugar levels] and pancreatic beta-cell secretory function' improve. <tt>2178</tt><tt>2179</tt>

Such studies implicate inflammation as, at least, a contributor to insulin resistance.

In 2006, researchers examined gene expression in the subcutaneous adipocytes, of 45, obese and insulin-resistant participants and obese and insulin-sensitive participants.

They found higher expression of pro-inflammatory genes in the group considered obese and insulin-resistant.<tt>2051</tt>

Though it is important to note obese patients who remain insulin-sensitive are likely in a transient phase rather than a settled state of "lesser harm”.

Similar conclusions, associating obesity with inflammation, are also made in studies which directly measure and observe higher circulating inflammatory cytokines in obese participants in comparison to "healthy" participants.

The bigger picture suggests obesity adversely affects each organ system in different ways. Though inflammation is only part of the story, the activity of excess food intake is a root cause.

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2. Chronic Sleep Deprovision

The physiological changes following chronic sleep deprivation are increasingly being linked to a host of diseases, most notably cardiovascular disease.

A large prospective cohort study published in 2019 involved studying the health profile (including the sleeping habits) of 60,586 Taiwanese participants between 1996 and 2014.

During follow-up, 4.5% of participants experienced a new coronary artery disease event, which was statistically significantly more associated with those experiencing poor sleep duration and/or quality.^{<tt>2154</tt>}

Further research supports an association between sleep quality and subclinical vascular changes, notably carotid artery intima media thickness (IMT) which 'has been used to study subclinical atherosclerosis, and is widely adopted as a surrogate marker for predicting cardiovascular disease (CVD)'.

A 2013 cross-sectional study tracked the sleeping quality of 257 police officers from the Buffalo Police Department, New York, between 2004 and 2009 using objective data from sleep-tracking wristwatches.

Analysis of the data suggests 'Officers who had fewer than 5 [hours] or 8 hr or more of objectively measured sleep duration had significantly higher maximum artery intima media thickness (IMT) values'.

Several possible mechanisms exist which could explain the association between cardiovascular disease and sleep deprivation, one of which is chronic low-grade inflammation.

This is supported by a 1999 observational study which shows increased markers of inflammation (most notably interleukin-6) even after a single night of sleep deprivation.^{<tt>2152</tt>}

A 'follow-up' 2004 interventional study by the same authors involved 25 participants being sleep-deprived for 12 consecutive nights, after which they were subjected to psychomotor testing.^{<tt>2153</tt>}

Interestingly, in sleep-deprived individuals, inflammatory markers were higher than baseline during the daytime but lower than baseline during the nighttime.

The authors suggest this pattern may either explain or result from the increased time sleep-deprived individuals spend in the deepest stages of sleep.

Notably, the magnitude of IL-6 elevation after repeated sleep deprivation was comparable to that observed after a single night of sleep loss observed in prior studies, suggesting that the consistency of inflammation—rather than its magnitude—may be more closely linked to the development of disease.

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3. Dormant Infections

Helicobacter pylori (H. pylori) is one of the most ubiquitous human infections, with an estimated 43.9% of the global adult population infected between 2015 and 2022.

This figure ranges widely, estimated at 17.6% in the United States and as high as 54.9% in South Korea.^{<tt>2158</tt>}

Initially, it is spread by consuming contaminated water or food or by contact with a contaminated person.

However, many of these cases are asymptomatic, and some persist following a prior active infection having not been fully eradicated—commonly due to incomplete, ineffective or resistant antibiotic treatment.^{<tt>2166</tt>}

Under stressful conditions—such as antibiotic exposure or the acidity of the gastric milieu—the bacterium can transition from its spiral ("active") form to an enigmatic, coccoidal ("dormant") form.^{<tt>2159</tt>}

This morphological shift has important clinical implications. The coccoidal ("dormant") form is less metabolically active and significantly less pathogenic, meaning it is often asymptomatic.^{<tt>2159</tt>}

As a result, a substantial proportion of infected individuals may be unaware of their infection.

Furthermore, the coccoidal ("dormant") form is generally not detectable with the urea breath test (UBT), the standard test used to diagnose the spiral ("active") form. Instead, the most reliable diagnostic tool is immunohistochemistry of a gastric mucosa biopsy sample.^{<tt>2181</tt>}

The standard and effective triple therapy antibiotic course for spiral ("active") H. pylori may be much less effective against the coccoidal ("dormant") form of H. pylori.

More gravely, it is estimated 77.3% of worldwide gastric cancers, in 2018 at least, were attributed to H. pylori infection.^{<tt>2161</tt>}

In a 2019 retrospective cohort study, among the 371,813 participants diagnosed with an H. pylori infection, 0.54% went on to develop gastric cancer (adenocarcinoma). ^{<tt>2162</tt>}

The lifetime risk factors are highest in East Asia, which accounts, astonishingly, for over half the world's burden of gastric cancer.^{<tt>2182</tt>}

In many cases, a mix of risk factors (e.g., nitrate-rich diet, smoking, and immune compromise) gave the dormant form an opportunity to shift to an active form and, consequently, thrive.

It is widely accepted that chronic gastritis (inflammation of the gastric lining) is a significant contributor to the development of gastric cancer; this mechanistic link is known as Correa Cascade.^{<tt>2164</tt> <tt>2165</tt>}

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4. Smoking/ Vaping

In the context of substitution for tobacco smoking, a delicate balance should exist in criticising e-cigarettes and vapes, as they are widely considered less pathogenic than consuming tobacco, but are themselves associated with adverse health effects (e.g., asthma and lung irritation).

In trying to tease out to what extent smoking and vaping were independently responsible for symptoms of respiratory distress and disease, researchers combed through the literature before deciding to review 119 studies related to the topic in elucidative detail.<tt>2172</tt>

Findings indicate "non smoker current vapers" had a 'significantly higher incident risk compared to never users' in relation to respiratory symptoms (e.g., cough, phlegm, wheezing, or shortness of breath).

However, "non smoker current vapers" also had significantly lower incident risk compared to "non-vaper current smokers...' following at least short-to-medium-term exposure to the same symptoms.

Researchers also found a statistically significant association between "non-smoker current vapers" and a higher risk of lung inflammation and damage compared to "non-users" (i.e., those who quit vapers and/or smokers).

This respected 2025 review is unique because the researchers were able to isolate the risk of vaping, by studying users who never previously smoked tobacco and comparing their outcomes to those who never used either and to those who only recently ceased.

This important methodological approach avoids confounding the long-term effect of tobacco smoking with the outcomes related to vaping among those who smoke and vape.

Earlier evidence supports these conclusions at a molecular level.

Back in 2019, an observational cross-sectional study involved directly comparing over 50 unique markers of inflammation and inflammation-associated biomarkers in vapers and non-vapers.<tt>2168</tt>

For comprehensive purposes, those biomarkers were tested in several biological fluids: plasma, urine, saliva and exhaled breath condensate (EBC), with almost half of biomarkers observed to be adversely abnormal compared to the normal group.

Specifically, plasma concentrations of the pro-inflammatory cytokines IL-6, IL-8 and IL-13 were significantly elevated, while IL-1β was significantly increased in saliva. Anti-inflammatory mediators like resolvin D1 and resolvin D2 were reduced, suggesting an impact on the body's ability to resolve inflammation.

Together, these findings indicate that vaping induces measurable biological stress and inflammatory responses, not just in the lungs, but potentially systemically.

While such molecular changes do not always translate immediately into clinical disease, they could be a mechanistic explanation for the respiratory symptoms observed in epidemiological studies.

The most serious effects of vaping may play out over a longer timeframe, and since vapes have only been widely available in the last 15 years, as longitudinal data continue to emerge, a clearer picture of the chronic risks associated with vaping is likely to develop.

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5. Psychological Stress

Stress often appears as an inconspicuous feature in modern life.

Among the many sources of psychological stress, occupational stress has been widely cited as one of the most prominent. More specifically, this is the case within the teaching profession, which is regarded as one of the most mentally demanding occupations, reflected in high turnover and early retirement rates.

These rates might be a reflection of the biological effect stress inflicts on the human body.

A 2023 systematic review of studies on the teaching profession and stress found that most studies reported a statistically significant link between chronic stress in teachers and abnormal cortisol levels – commonly used as a biological marker of stress.^<tt>2173

Cortisol, the endogenous glucocorticoid on which anti-inflammatory medications such as hydrocortisone are based, helps regulate inflammation by altering gene expression in immune cells, ultimately suppressing cytokine-mediated inflammation.

Recent evidence suggests the concentrations of cortisol deposited in hair follicles serve as a more reliable reflection of cumulative cortisol levels over preceding months, in contrast to salivary measurements, which fluctuate over minutes to hours.^{<tt>2183</tt>}

This revelation is incredibly convenient for studying the associations related to chronic stress.

One longitudinal study, involving 41 teachers, with data collected over approximately one year, found hair cortisol concentration was correlated with factors such as workload, disruptions and student aggression. ^{<tt>2177</tt>}

Understanding the triggers of stress might give opportunity for preventative action, preserving long-term health, particularly since high stress levels could make the immune system more vulnerable.

When researchers examined how chronic stress affects the immune system by measuring levels of natural killer (NK) cells of 347 Japanese white-collar workers, they found that participants’ ratings of two factors—“respect and support” and “job promotion and salary”—were correlated with NK cell concentrations in the body.^{<tt>2175</tt>}

Meaning, participants, who scored these factors low as a reflection of their experience in their occupation, showed a lower concentration of NK cells, the immune defence cells.

These findings may help explain results from a 2013 study, in which researchers observed that teachers who reported an effort–reward imbalance (ERI) at work had higher levels of inflammatory markers, particularly increased concentrations of IL-6 when their blood samples were stimulated under laboratory conditions (in vitro).^{<tt>2176</tt>}

The body of evidence reflects the understanding that traumatic experiences are not only processed cognitively but are also encoded within the body, influencing physical sensations, physiological responses, and long-term health.

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Conclusion

Chronic inflammation is not the only mechanism linking these risk factors to disease, but it is an important connecting pathway.

Obesity, sleep deprivation, dormant infection, vaping or smoking, and psychological stress each place different pressures on the body, yet all can activate inflammatory processes that accumulate over time.

The evidence suggests that disease often develops gradually, through repeated biological strain rather than a single event.

Recognising this shared mechanism helps shift attention from treating illness after it appears to reducing the exposures that drive it.

Protecting long-term health therefore requires addressing both visible behaviours and less obvious physiological burdens.