IL-6 genetic variants, levels, and longevity

Interleukin-6 (IL-6) is a cytokine, a small protein that circulates in the blood and plays a role in inflammation and energy homeostasis. It is produced by various immune cells as well as adipocytes (fat cells). It is required for a properly functioning immune system, recovery from exercise, and signaling to the body that you are full. However, too much of it can lead to unhealthy inflammatory states. People with genetic variants that result in a lower overall IL-6 levels have longer lifespans and less cardiovascular disease on average, but at the expense of more asthma and dermatitis.

IL-6 and inflammation and obesity (negative IL-6 effects)

You may have heard of IL-6 in the news for being a “bad-actor” in promoting the harmful effects of cytokine storm in severe COVID-19 infections. A drug that lowers IL-6 signaling is approved for COVID-19 hospitalized patients.

IL-6 production by fat cells is thought to be a reason why obese individuals have higher endogenous levels of C-reactive protein (CRP). CRP, a well known markers of inflammation, is produced by the liver in response to signaling by circulating IL-6.

IL-6 and exercise (positive IL-6 effects)

During exercise and recovery, IL-6 acts as an energy sensor and helps regulate energy metabolism. It plays a role in muscle repair and adaptation, contributing to the process of becoming stronger after physical activity. IL-6 signaling can influence glucose and fatty acid metabolism, contributing to energy homeostasis during the post-exercise period.

Higher intensity and longer exercise bouts lead to greater increases in IL-6. Adequate rest and proper nutrition are crucial for adaptation and recovery after exercise. Insufficient energy intake or excessive activity can lead to sustained high levels of IL-6. With regular training, the IL-6 response to exercise is often attenuated, and resting levels may decrease over time.

IL-6 and GLP-1 (positive IL-6 effects)

Studies in experimental animals indicate that IL-6 in the CNS partly mediates the suppression of food intake and body weight exerted by glucagon-like peptide-1 (GLP-1) receptor stimulation. GLP-1 is the peptide in the weight loss drugs, Ozempic and Wegovy.

Outside of the Central Nervous System, it seems that IL-6 stimulates the production of GLP-1 in the endocrine pancreas and the gut.

These mechanisms mean that increases in IL-6 can be positive for weight loss through affecting GLP-1 signaling.

IL-6 genetic variants decrease its levels and are associated with longer lifespan

A meta-analysis (analysis of all studies) showed that IL-6 genetic variants that associate with decreased levels of IL-6 are related to longer lifespan in Italian men. In women and other European people, this did not bear out. However, more study is needed with larger sample sizes.

A causal AI study showed that people with less plasma IL-6 were less likely to have cardiovascular disease, stroke, and rheumatoid arthritis, and lived longer. However, this was at the expense of being more likely to have atopic dermatitis and asthma.

If you have had NeuroAge genetic resilience testing, you can see whether you have IL-6 genetic variants that results in lower levels.

IL-6 inhibitors

As of September 2025, the U.S. FDA has approved four interleukin-6 (IL-6) inhibitors:

• Tocilizumab (Actemra): An antibody that targets the IL-6 receptor. It is approved for multiple conditions, including rheumatoid arthritis, giant cell arteritis, and COVID-19 in hospitalized patients.

• Sarilumab (Kevzara): An antibody that targets the IL-6 receptor. It is indicated for treating adults with moderately to severely active rheumatoid arthritis and polymyalgia rheumatica, as well as polyarticular juvenile idiopathic arthritis.

• Siltuximab (Sylvant): An antibody that binds directly to the IL-6 cytokine. It is approved for the treatment of patients with multicentric Castleman's disease.

• Satralizumab (Enspryng): An antibody that targets the IL-6 receptor. It was approved in 2020 for the treatment of neuromyelitis optica spectrum disorder.
  

A causal AI study (DrugMR) analyzed people who were taking IL-6 inhibitors and their incidence of other disorders to identify what other conditions may benefit from IL-6 inhibition. IL-6 inhibitors significantly reduced the risk of idiopathic pulmonary fibrosis, Parkinson’s disease, and Type 2 diabetes. However, these inhibitors increased the risk for asthma and asthmatic pneumonia, consistent with the genetic studies of people with IL-6 variants. The authors found no relationship to Alzheimer’s disease, Crohn’s disease, pulmonary heart disease, systemic lupus erythematosus, Type 1 diabetes, Non-small cell lung cancer or ulcerative colitis.

How to decrease your IL-6 levels

While acute exercise can temporarily increase IL-6, consistent physical activity leads to chronically lower basal IL-6 levels, which is beneficial for long-term health. Maintain a healthy weight as obesity is associated with chronic, low-grade inflammation, and weight loss can significantly decrease IL-6 levels.

A Mediterranean-style diet, which is rich in anti-inflammatory foods, is associated with lower IL-6 levels. High fat meals, but not high carbohydrate meals, increase IL-6.

A systematic review and meta-analysis of 99 publications, found that massage was a powerful way to reduce IL-6 and CRP post-exercise.

You can track your IL-6 levels through a testing service like Quest Diagnostics.