Scientists Uncover a New Way to Pinpoint Inflammation in the Body

• Your body’s first line of defense — When you get injured or are exposed to harmful bacteria, your immune system jumps into action. Specialized immune cells called macrophages act like sentries, constantly patrolling your body. They detect distress signals from damaged cells or foreign invaders and respond quickly to keep you safe.⁴

• Cellular “alarms” trigger an immune response — When your immune system detects a threat, it sounds the alarm by releasing signaling molecules called cytokines and chemokines. These act like emergency alerts, calling in more immune cells to help. Cytokines also control how strong and long-lasting the inflammation is, making sure your body responds appropriately.⁵

• Increased blood flow fuels the battle — When your immune system detects a threat, your blood vessels widen to increase blood flow to the area. This delivers immune cells, including neutrophils, which attack invaders and clear out damaged tissue. Along with oxygen and nutrients, this surge helps fight infection and start the healing process, causing redness, swelling, and warmth, the classic signs of inflammation.⁶

• Immune cells attack and clear the threat — When your body detects a threat, neutrophils are the first to arrive. They quickly engulf harmful particles and release antimicrobial substances to kill invaders. If the threat persists, macrophages take over, clearing pathogens and cellular debris, while T-cells coordinate the immune response and destroy infected cells to prevent further damage.⁷

• Shutting down inflammation for recovery — Once the infection or injury is under control, your immune system releases anti-inflammatory molecules to slow down the response. This prevents unnecessary damage to healthy tissue and helps your body transition from defense to repair.⁸

• A unique chemical reaction enables detection — Researchers found that when reactive oxygen species (ROS) — highly reactive molecules that damage DNA, proteins, and lipids — interact with certain compounds, they create a distinct chemical reaction. This reaction leaves a detectable marker, allowing antibodies to track inflammation at its source.¹¹

• The role of reactive oxygen species — During inflammation, your immune cells release ROS to kill bacteria and fight infections. These molecules also come from environmental sources like UV light, pollution, radiation, and smoking. While ROS helps protect you, too many damages your cells and tissues and contributes to disease.¹²

• How ROS interact with fats in your cells — Researchers found that ROS reacts with linoleic acid, a type of omega-6 fat in all cell membranes. This interaction creates compounds called epoxyketooctadecanoic acids (EKODEs), which attach to RNA, DNA, and proteins, leaving behind markers that detect inflammation.¹³

• A breakthrough in biomarker detection — The study also found that EKODEs form a unique bond with cysteine, a nucleic acid. These compounds build up in tissues under oxidative stress, including the brain, heart, and liver. By creating antibodies to detect EKODEs in mouse models, they successfully identified these markers in both mice and humans, paving the way for more precise inflammation detection.¹⁴

• Linking EKODEs to disease — The researchers now aim to map EKODEs to specific diseases by identifying which organs and conditions these markers are most strongly associated with. One area of focus is the eye, where EKODEs play a role in age-related macular degeneration and diabetic retinopathy, both of which lead to vision loss.¹⁵

• EKODEs are double-edged signalers — EKODEs (epoxy-keto fats) feature both an epoxide ring and a keto group, giving them distinct bioactive properties. At low concentrations, EKODEs activate pathways that influence antioxidant defenses, inflammation, and metabolism. Studies suggest they dampen inflammation in vascular tissues, and even modulate pain responses.

However, when levels spike during oxidative stress, like in chronic disease, they become damaging, attacking proteins, disrupting membranes, and amplifying cellular dysfunction. In short, they act as pivotal mediators in inflammation, tipping the balance between adaptation and damage.

• 4-HNE is a potent messenger of stress — 4-HNE is a highly reactive aldehyde that activates Nrf2 to boost detoxification enzymes. It can also increase cytokines, your body’s inflammatory alarm system. At low levels, 4-HNE acts as a signaling molecule that promotes cellular adaptation.

At high levels, 4-HNE shifts to a destructive role, binding to mitochondrial proteins, triggering apoptosis, and fueling different diseases, from Alzheimer’s to atherosclerosis. Its electrophilic nature lets it “tag” proteins on cysteine or lysine residues, altering their function in ways that either support survival or accelerate cellular dysfunction. In inflammation, 4-HNE is a key driver that shapes both the magnitude and trajectory of the response.

• MDA is the silent cross-linker — Malondialdehyde, the dialdehyde cousin, plays a less overt but equally damaging role in oxidative stress. MDA excels at cross-linking proteins and DNA, leaving a trail of damage. It’s less a direct signaler and more a saboteur, quietly amplifying inflammation by compromising your cellular machinery.

Although it influences stress pathways indirectly, its real danger lies in chronic accumulation — think diabetes, aging, or cancer — where it erodes structural integrity. MDA’s presence is a red flag signaling unresolved long-term oxidative stress.

• The interplay between these three compounds — These three lipid-derived compounds don’t act independently. During oxidative stress, they interact within the same biochemical environment, competing for nucleophilic targets — cysteines and lysines on proteins — and diluting each other’s effects. For example, if 4-HNE tags a key enzyme first, it blocks subsequent interactions by EKODEs.

In high-stress states (say, a heart attack or chronic infection), they synergize and overwhelm antioxidant defenses like glutathione. 4-HNE compromises mitochondria, MDA cross-links DNA, and EKODEs destabilize membranes, creating a perfect storm of inflammation and damage. However, at lower levels, EKODEs upregulate detox enzymes, which curbs 4-HNE’s and MDA’s effects, and offers a protective counterbalance.

• Why this matters to you — The behavior of these compounds serves not just as a scientific explanation but as a roadmap. These lipid peroxidation products are measurable (via assays like TBARS for MDA or mass spectrometry for 4-HNE), and their levels reflect your oxidative load. The diagnostic approach discussed in this article could, in theory, spotlight their activity indirectly. Think of it as a window into their influence on your inflammatory response.

The good news is that these lipid peroxidation products are factors you can influence. Understanding how they interact equips you with the knowledge to detect inflammation and address it at its roots. To tip the scales in your favor, support Nrf2 activation with sulforaphane-rich foods like broccoli sprouts, fight ROS with polyphenols from sources such as green tea, and reduce omega-6 overload by eliminating vegetable oils from your diet.

• Inflammation vs. unalamation — Experts have long believed that chronic inflammation happens because the immune system stays too active. However, researchers now suggest that it results from a loss of anti-inflammatory mediators, disrupting a balance called unalamation. This challenges the conventional idea that suppressing inflammation is the ideal treatment.¹⁹

• The role of unalamation in health and disease — Your body uses inflammatory mediators like prostaglandins and cytokines to fight infections, heal wounds, and maintain tissues. Unalamation is the balance between these inflammatory and anti-inflammatory signals. When anti-inflammatory mediators drop too low, inflammation persists, even without an injury or infection, leading to long-term health problems.²⁰

• Why standard anti-inflammatory drugs fall short — NSAIDs and other inflammation-blocking drugs help with short-term inflammation but don’t fix chronic conditions like arthritis, heart disease, or neurodegenerative disorders. This is because they block inflammatory signals without restoring the missing anti-inflammatory ones, leaving the underlying imbalance unaddressed.²¹

• Cancer and the unalamation connection — Researchers are also rethinking the idea that chronic inflammation drives cancer. Tumors contain both inflammatory and anti-inflammatory signals, which suggests that they grow in a state of heightened unalamation, not just inflammation. This may explain why blocking inflammation alone doesn’t stop cancer and targeting unalamation could lead to better treatments.²²

1. Excess LA — An omega-6 polyunsaturated fat (PUFA), LA is found abundantly in vegetable oils and ultraprocessed foods. LA is one of the most harmful ingredients in the Western diet. When consumed in excessive amounts, it negatively affects your metabolic rate and gut microbiome, which are two of the most important factors for maintaining proper inflammatory responses and overall health.

2. Electromagnetic fields (EMFs) — EMFs are generated by everyday electronic devices such as cell phones, Wi-Fi routers, and microwaves, causing unseen harm to your health. EMFs activate voltage-gated calcium channel (VGCC) receptors in your cells, leading to an influx of calcium ions. This surge in calcium catalyzes the production of peroxynitrite, a potent oxidant that contributes to cellular stress and inflammation.²³

3. Endocrine-disrupting chemicals (EDCs) — Exposure to EDCs significantly impacts your health by over-activating estrogen receptors in your body. Microplastics are alarmingly prevalent in our environment, with research suggesting that the average person ingests the equivalent of a credit card’s weight in plastic each week.²⁴

Plastic is often laden with harmful substances like phthalates and bisphenol A (BPA), both of which bind to estrogen receptors and disrupt normal hormonal functions. Elevated estrogen increases intracellular calcium levels,²⁵ which leads to the generation of peroxynitrite. This exacerbates inflammation and plays a role in various chronic health conditions.

4. Endotoxins — Consuming ultraprocessed foods loaded with vegetable oils and high-fructose corn syrup (HFCS), as well as exposure to EDCs, disrupts your gut microbiome, increasing endotoxin production and systemic inflammation. Endotoxins are toxic substances released from the cell walls of certain bacteria, particularly gram-negative bacteria.

These bacteria are facultative anaerobes, meaning they thrive in both aerobic (with oxygen) and anaerobic (without oxygen) environments. This adaptability allows them to colonize various areas in the body, including the gut, where they contribute to inflammation.

When endotoxins from these bacteria enter the bloodstream — often due to a compromised gut barrier (leaky gut) — they trigger a strong inflammatory response known as endotoxemia. This condition is linked to various health issues, including metabolic syndrome and autoimmune diseases.