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Chronic Inflammation: The Root of All Diseases
23 Jun at 4:20 pm
Chronic inflammation, spanning conditions like cardiovascular issues, diabetes, mental health disorders, cancer, and chronic liver disease, holds the potential to be deemed as the underlying cause of various ailments. The significance of adopting an anti-inflammatory treatment approach and cultivating a lifestyle that proactively mitigates inflammation cannot be overstated for the maintenance of optimal health.
Typically, in instances of infection or injury, the body’s inflammatory response is localized and of short duration, falling under the category of acute inflammation. However, the prevailing social environment and lifestyle choices have the capacity to instigate systemic chronic inflammation (SCI). This persistent state forms the foundation for a spectrum of health challenges, including cardiovascular diseases, cancer, diabetes, chronic nephritis, non-alcoholic fatty liver, autoimmune disorders, and degenerative diseases.
As scientific understanding has progressed, there has been a gradual realization of the profound impact that systemic chronic inflammation exerts on various body tissues.
Origins and Ramifications of Low-Level Systemic Chronic Inflammation
The definition of inflammation
Inflammation, fundamentally a defense mechanism against the infiltration of harmful substances into the body, unfolds as the activation of immune cells and other non-immune cells. Its purpose is to shield the host from bacteria, viruses, toxins, and infections by eradicating pathogens and fostering tissue repair and recovery.
While inflammation is a crucial component for maintaining homeostasis in normal humans throughout childhood and adulthood, age-related diseases such as cardiovascular disease, diabetes, cancer, and Alzheimer’s disease often share chronic inflammation as a common pathological foundation. This inflammatory state may serve as a pivotal factor contributing to the escalation of morbidity and mortality in numerous degenerative conditions.
A standard inflammatory response is temporal, marked by activity that ensues while a threat is imminent and recedes once the threat subsides.
The term “systemic chronic inflammation” (SCI) delineates a low-grade noninfectious state, often referred to as “sterile.” This state arises due to specific extrinsic factors (social, psychological, environmental) and biological elements associated with the resolution of acute inflammation. Characterized by the activation of immune cells, the immune components at play in SCI differ from those observed during acute disease. This prolonged inflammatory condition is implicated in the development of several diseases, contributing significantly to global disability and mortality rates, surpassing 50%. Conditions linked to SCI include cardiovascular disease, cancer, diabetes, chronic kidney disease, nonalcoholic fatty liver disease, as well as autoimmune and neurodegenerative diseases.
The transition from short-term to long-term alterations in the inflammatory response precipitates a breakdown of immune tolerance. This process leads to substantial changes in all tissues, organs, and normal cellular physiology, thereby amplifying the susceptibility to various non-communicable diseases in both the young and the elderly.
Association Between Chronic Inflammation and Non-Communicable Diseases
The impact of systemic chronic inflammatory damage tends to escalate with age, with studies indicating elevated levels of circulating cytokines, chemokines, and acute-phase proteins in older adults.
Systemic chronic inflammation is characterized by low-grade persistent inflammation that can result in tissue and organ damage through processes such as oxygen stress. The clinical ramifications are severe, contributing to a spectrum of chronic diseases, encompassing insulin resistance, cardiovascular disease, pulmonary hypertension, chronic obstructive pulmonary disease, emphysema, Alzheimer’s and Parkinson’s diseases, macular degeneration, bone arthritis, and cancer.
Markers commonly associated with acute inflammation may not be directly applicable to systemic chronic inflammation. Notably, earlier research by Roubenoff and colleagues demonstrated an age-related increase in circulating levels of IL-6 and IL-1Ra, while IL-1β or TNF-α did not exhibit similar patterns. However, when the health status of the elderly was rigorously controlled, no discernible differences in the expression of IL-1 and IL-6 between young and old individuals were observed. Presently, there are no established biomarkers specifically indicative of systemic chronic inflammation.
Understanding the Origins of Chronic Inflammation
As individuals age, the immune system attains its peak in young and middle-aged individuals before gradually aging. The systemic chronic inflammatory state observed in the elderly is, in part, attributed to cellular senescence. This state is marked by the cessation of cell proliferation and the emergence of multiple senescence-associated secretory phenotypes (SASP).
A notable feature of SASP is the heightened secretion of pro-inflammatory cytokines, chemokines, and other molecules with pro-inflammatory properties. Cells exhibiting this senescent phenotype can contribute to a diverse array of chronic diseases, including insulin resistance, cardiovascular disease, pulmonary hypertension, chronic obstructive pulmonary disease, emphysema, Alzheimer’s and Parkinson’s diseases, macular degeneration, osteoarthritis, and cancer.
The mechanisms through which senescent cells produce SASP are not fully elucidated, but ongoing research suggests a combination of endogenous and exogenous factors. Social, environmental, and lifestyle risk factors, whether inherent or external, are believed to play a role in the onset and progression of SASP.
Understanding the Factors Influencing Chronic Inflammation
The origins of chronic inflammation are multifaceted, involving a complex interplay of endogenous and exogenous factors that contribute to the progression of systemic chronic inflammation (SCI). Here, we explore the diverse causes, consequences, and associations related to low-level systemic chronic inflammation.
- Endogenous Factors
These intrinsic factors encompass various elements within the body, including DNA damage, abnormal telomere function, epigenome disruption, abnormal mitotic signaling, and oxidative stress.
- Exogenous Causes
External factors play a pivotal role in the development of SCI. These include chronic infections, lifestyle-induced obesity, microbiome dysbiosis, dietary choices, social and cultural changes, and exposure to environmental and industrial toxins. While studies have shown limited associations between these risk factors and systemic chronic inflammation, they remain significant contributors, particularly in older adults where differences among individuals highlight the importance of pro-inflammatory factors.
- Chronic Infection: Lifelong infections, such as those caused by cytomegalovirus, Epstein-Barr virus, hepatitis C virus, and other agents, have been debated for their impact on systemic chronic inflammation and immune dysregulation. Although chronic infection contributes to SCI, it is not considered a predominant factor. Traditional agricultural communities, with high microbial exposure and minimal industrial contact, exhibit remarkably low levels of systemic chronic inflammation that do not escalate with age.
- Lifestyle, Social, and Natural Environment: The relatively shorter life expectancy in agricultural countries is attributed not to genetics or reduced lifespan but to the distinct social and natural environment. Factors such as increased outdoor activity, diets rich in fresh or minimally processed foods, and limited exposure to environmental pollutants contribute to lower levels of systemic chronic inflammation. The shift with industrialization, while bringing numerous benefits, has also led to lifestyle changes that contribute to chronic inflammation, creating an evolutionary mismatch between humans and their environment.
- Physical Inactivity: Industrialization has resulted in a significant reduction in overall physical activity globally, with approximately 31% of people worldwide being inactive. Skeletal muscle, functioning as an endocrine organ, secretes cytokines during contraction, which may mitigate systemic inflammation. Physical inactivity, prevalent in high-income countries, is directly associated with increased anabolic resistance, elevated CRP levels, and higher pro-inflammatory cytokine levels. The consequences include an augmented risk of cardiovascular diseases, type II diabetes, nonalcoholic fatty liver disease, osteoporosis, various cancers, depression, dementia, and Alzheimer’s disease.
- Gut Flora Imbalance: Obesity contributes to chronic inflammation through mechanisms involving the gut microbiota. Changes in gut microbiota composition and gene richness correlate with increased fat mass, pro-inflammatory biomarkers, and insulin resistance. Disruptions in the delicate balance of the gut ecosystem, triggered by factors like antibiotic misuse, NSAIDs, proton pump inhibitors, and dietary choices, may lead to chronic inflammation.
- Diet: The dietary shift over the last four decades, characterized by a lack of fruits, vegetables, and fiber-rich foods and an increase in refined grains, alcohol, and ultra-processed foods, alters gut microbiota composition. This shift is associated with increased gut permeability, epigenetic changes in the immune system, and subsequent low-grade endotoxemia and chronic inflammation. Dietary components like trans fatty acids and excessive table salt further contribute to inflammation-related pathophysiological changes.
- Social and Cultural Change: Apart from exercise and dietary factors, changes in social interaction, sleep quality, and modern work environments contribute to chronic inflammation and insulin resistance. Elevated cortisol due to chronic stress disrupts the body’s ability to regulate inflammatory activity. Increased exposure to blue light, especially at night, disturbs circadian rhythms, promoting inflammation and raising the risk of inflammation-related diseases, including obesity, type 2 diabetes, cardiovascular diseases, and various cancers.
- Environmental and Industrial Toxic Substances: The rapid urbanization of the past two centuries has exposed humans to a myriad of exotic threats, including air pollutants, industrial hazardous waste, and chemicals that promote chronic inflammation. Thousands of new chemicals introduced annually are implicated in inflammation and inflammation-related diseases. Smoking, a pervasive external threat, closely ties to various inflammation-related diseases, contributing to the overall burden of chronic inflammation.
Understanding the intricate web of factors contributing to chronic inflammation is crucial in developing effective strategies for prevention and intervention. The interconnected nature of these elements highlights the need for a comprehensive, multidimensional approach to mitigate the impact of chronic inflammation on overall health and well-being.
