Inflammatory Disorders and Diseases

Introduction

Inflammation is the process by which the body’s immune system identifies and removes harmful stimuli. When the body activates the immune system, it recruits inflammatory cells. These cells attack foreign bodies and heal damaged tissue. The result can be pain, swelling, redness, and a rise in temperature at the healing site. However, when the immune system remains active even after the resolution of the infection or injury, it leads to chronic inflammation. Chronic (long-lasting) inflammation is a symptom of many underlying diseases.

What Are the Mechanisms Underlying Inflammatory Disorders and Diseases?

Chronic low-grade inflammation contributes to the disease mechanism of many inflammatory diseases. It is based on two established findings.

• Immune Dysregulation: During inflammation, the immune system protects the organism from injury by the production of inflammatory mediators. However, stress hormones may facilitate inflammation under certain conditions. Thus, a dysfunctional immune response is associated with the hyperactivity of the local pro-inflammatory factors. As a result, it may play a role in the pathogenesis of various chronic inflammatory disorders.

• Altered Redox Status: Redox (reduction and oxidation reactions in the body) imbalance is caused by a weakened antioxidative defense system. Also, there is an increase in reactive oxygen species (ROS) and free radicals that cause further injury.

Overproduced and unregulated ROS (also called oxidative stress) are a major causative factor in the activation of immune systems. Therefore, unresolved chronic inflammation may be a cause of many degenerative diseases.

What Are the Risk Factors Associated With Inflammatory Disorders and Diseases?

Several risk factors that promote inflammatory disorders include:

• Age: Increasing age positively correlates with elevated inflammatory molecules. The increase in inflammatory molecules may be due to free radical accumulation and other related factors.

• Obesity: Many studies report that fat tissue secretes multiple inflammatory mediators.

• Diet: A diet rich in fat or refined sugar leads to increased production of pro-inflammatory molecules.

• Smoking: Cigarette smoking is linked to inflammation and secreting pro-inflammatory molecules.

• Stress: Physical and emotional stress leads to inflammatory cytokines release.

What Are the Various Inflammatory Disorders and Diseases?

Evidence indicates that unresolved inflammation plays a significant role in modulating various diseases, such as obesity, dementia, atherosclerosis, cancer, and osteoporosis. As a result, the close involvement of inflammation in these diseases has led them to be named “inflammatory diseases.” Although the precise inflammatory involvement of each disease may vary, the mechanisms are similar.

• Obesity and Metabolic Syndrome: The prevalence of obesity is increasing in all populations worldwide. Hence, the epidemic rise of obesity has soared the interest of researchers in metabolic syndrome. Metabolic syndrome characterizes abdominal obesity, elevated triglycerides (TGs, lipids circulating in the body), reduced levels of good cholesterol (HDL, high-density lipoproteins), high blood pressure, and high fasting glucose. The inflammatory response occurring with obesity is triggered and initially maintained by adipose (fatty) tissue. Then, the systemic effects take place in the complications related to inflammation and obesity by the involvement of other metabolic sites (muscles and blood vessels). Studies suggest that obesity may promote the ingress of macrophages (immune cells) in the adipose tissue. Further, the macrophages may cause dysregulation in adipose tissue properties and enhance the production of inflammatory cytokines.
• Dementia: Inflammatory processes are related to the development of dementia (memory loss). Several pro-inflammatory markers are increased in dementia and cognitive decline. Inflammatory responses also modulate the pathogenic processes in AD. Various inflammatory markers increase with the onset of AD, such as interleukins, tumor necrosis factors, clotting factors, and activated microglia cells (brain immune cells). Therefore, dementia is linked to chronic inflammation that might be an important contributor to neurodegenerative disease development.
• Atherosclerosis: The primary contributor to cardiovascular disease (CVD) is atherosclerosis (which affects large arteries and is characterized by the accumulation of lipids in their walls). Inflammation plays a crucial role in all the phases of atherosclerosis. The activation of inflammatory cells (that is, macrophages, T lymphocytes) and smooth muscle cells is associated with the release of adhesion molecules, cytokines, and growth factors. IL-6 is a pro-coagulant (promotes clotting) and pro-inflammatory cytokine. IL-6 increases plasma concentrations of fibrinogen (a clotting protein) and C- reactive protein (CRP). These pro-inflammatory mediators are involved in atherosclerosis pathogenesis.
• Cancer: Carcinogenesis (cancer formation) is a multi-step process that includes initiation, promotion, and progression. It occurs as a consequence of cell proliferation and cell death imbalance. NF-κB (a group of immune proteins) is activated by stimuli, including pro-inflammatory cytokines, and plays a crucial role in carcinogenesis. The activation or expression of NF-κB is evident in breast cancer, thyroid cancer, stomach cancer, colon cancer, liver cancer, and blood cancer. Chronic inflammation with free radical generation can lead to events that cause malignant (cancerous) transformation. Initiated cells can be further promoted by NF-κB proteins induced by pro-inflammatory cytokines. Because activated NF-κB can inhibit apoptosis (cell death) and stimulate the production of pro-inflammatory cytokines, it further promotes the proliferation of initiated cells.
• Osteoporosis: Osteoporosis is a low bone mass condition resulting in impaired mobility and low quality of life (QoL). It has become a significant social and financial healthcare problem. The crucial role of the bone is to provide a rigid structure to support the body and protect essential organs. Hence, bone is actively re-constructed and remodeled by a lifelong turnover process. Chronic inflammation disrupts bone homeostasis (balance and function) and may increase the incidence of osteoporosis. Increased CRP levels have been shown to lower bone-mineral density in women. Further, CRP is consistently related to increased fracture risk in old women.

What Is the Treatment of Inflammatory Disorders and Diseases?

Current anti-inflammatory drugs are effective in treating inflammatory disorders and diseases.

• Supplements: Certain vitamins (vitamins A, C, and D) and supplements (zinc) may reduce inflammation and enhance repair as they act as antioxidants and reduce the generation of free radicals.

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): These medicines lower inflammation. The mechanism of action of NSAIDs is cyclooxygenase (COX) enzyme inhibition. COX-1 plays a role in maintaining stomach and intestinal mucosa lining, kidney function, and platelet aggregation. COX-2 is expressed during an inflammatory response. Hence, COX-2 selective NSAIDs provide anti-inflammatory relief with minimal side effects.

• Steroids: Corticosteroid injections decrease inflammation in a specific area due to their immunosuppressant property.

Conclusion

Chronic inflammation is a primary biological mechanism underpinning various inflammatory diseases. The key mediators of inflammatory diseases are upregulated during the aging process. The activation of the pro-inflammatory molecular network is implicated in numerous diseases, including dementia, cardiovascular disease, cancer, obesity, metabolic syndrome, and osteoporosis. Hence, a better understanding of inflammation may assist in future interventions to treat inflammatory diseases and disorders.