Inflammation is part of the body's defense mechanism. It is the process by which the immune system recognizes and removes harmful and foreign stimuli and begins the healing process. Inflammation can be either acute or chronic.
Tissue damage due to trauma, microbial invasion, or noxious compounds can induce acute inflammation. It starts rapidly, becomes severe in a short time and symptoms may last for a few days for example cellulitis or acute pneumonia. Subacute inflammation is the period between acute and chronic inflammation and may last 2 to 6 weeks.
Chronic inflammation is also referred to as slow, long-term inflammation lasting for prolonged periods of several months to years. Generally, the extent and effects of chronic inflammation vary with the cause of the injury and the ability of the body to repair and overcome the damage. This article reviews chronic inflammation.
Chronic inflammation can result from the following:
Chronic inflammatory diseases are the most significant cause of death in the world. The World Health Organization (WHO) ranks chronic diseases as the greatest threat to human health. The prevalence of diseases associated with chronic inflammation is anticipated to increase persistently for the next 30 years in the United States. in 2000, nearly 125 million Americans were living with chronic conditions and 61 million (21%) had more than one. In recent estimates by Rand Corporation, in 2014 nearly 60% of Americans had at least one chronic condition, 42% had more than one and 12% of adults had 5 or more chronic conditions. Worldwide, 3 of 5 people die due to chronic inflammatory diseases like stroke, chronic respiratory diseases, heart disorders, cancer, obesity, and diabetes. The prevalence of some specific chronic inflammation-mediated diseases are as follows:
Most of the features of acute inflammation continue as the inflammation becomes chronic, including the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability and migration of neutrophils into the infected tissue through the capillary wall (diapedesis). However, the composition of the white blood cells changes soon and the macrophages and lymphocytes begin to replace short-lived neutrophils. Thus the hallmarks of chronic inflammation are the infiltration of the primary inflammatory cells such as macrophages, lymphocytes, and plasma cells in the tissue site, producing inflammatory cytokines, growth factors, enzymes and hence contributing to the progression of tissue damage and secondary repair including fibrosis and granuloma formation, etc.
In response to foreign or self-antigens, the tissue immune cells such as macrophages and dendritic cells release cytokines such as IL-1 and TNF-α. These cytokines induce the injury-site-endothelial cells to release Selectins and Integrins which stimulate chemotaxis and diapedesis of the circulating leukocytes. In addition to the recruitment of leukocytes, the tissue macrophages, and dendritic cells also play a role in the clearing of the antigen by phagocytosis, the release of cytokines and serving as antigen-presenting-cells to lymphocytes. Once the circulating leukocytes enter the local injury site, they are activated by various cytokines and chemokines secreted by the macrophages and dendritic cells. On activation, the leukocytes further release cytokines and mediators of inflammation. Neutrophils are the initial cells and most predominant in the acute phase of inflammation. Neutrophils contain granules rich with lysozyme, matrix metalloproteinases, myeloperoxidase which are released on the foreign or self-antigen leading to its destruction. Neutrophils also destroy the antigen by phagocytosis, the release of reactive oxygen species and cytokines such as IL-1, IL-6, and TNF-α. Lymphocytes including T-lymphocytes and B-lymphocytes are the next line of defense, and they play a crucial role in mediating inflammation by several complex mechanisms including secreting of cytokines, costimulation of lymphocytes, and production of antibodies and immune complexes. Circulating platelets can also play a role in inflammation by platelet aggregation, thrombus formation and degranulation releasing chemokines and inflammatory mediators.
Types of Chronic Inflammation
Risk Factors Associated with Chronic Inflammation
Several risk factors promote a low-level inflammatory response. These include:
Symptoms of Chronic Inflammation
Some of the common signs and symptoms that develop during chronic inflammation are listed below.
Tests for Chronic Inflammation
Unfortunately, there are no highly effective laboratory measures to assess patients for chronic inflammation and diagnoses are only undertaken when the inflammation occurs in association with another medical condition.
Many dietary and lifestyle changes may be helpful in removing inflammation triggers and reducing chronic inflammation as listed below. The most effective is weight loss. For example, in patients with psoriatic arthritis which is chronic inflammatory arthritis, weight loss alone has been shown to be independently associated with clinically significant improvement in disease activity and inflammation.
In human clinical trials, it is shown that energy expenditure through exercise lowers multiple pro-inflammatory molecules and cytokines independently of weight loss.
Conventional Drugs that Combat Chronic Inflammation
Metformin is commonly used in the treatment of type II diabetic patients with dyslipidemia and low-grade inflammation. The anti-inflammatory activity of metformin is evident by reductions in circulating TNF-alpha, IL-1beta, CRP, and fibrinogen in these patients.
Statins are anti-inflammatory as they reduce multiple circulating and cellular biomediators of inflammation. This pleiotropic effect appears to contribute in part to the reduction in cardiovascular events.
Non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen, ibuprofen, and aspirin acts by inhibiting an enzyme cyclooxygenase (COX) that contributes to inflammation and are mostly used to alleviate the pain caused by inflammation in patients with arthritis.
Corticosteroids also prevent several mechanisms involved in inflammation. Glucocorticoids are prescribed for several inflammatory conditions including inflammatory arthritis, systemic lupus, sarcoidosis, and asthma.
Herbal supplements like ginger, turmeric, cannabis, hyssop, and Harpagophytum procumbens are shown to have anti-inflammatory properties however one should always consult with a doctor before their use and caution should be taken for using some herbs like hyssop and cannabis.
It is important to realize that chronic inflammation is not a specific disease but a mechanistic process. The diseases associated with chronic inflammation are multiple and include CVD, diabetes, malignancy, auto-immune disease, chronic hepatic and renal disease, etc. A good history, physical examination, and routine laboratory tests (glucose, creatinine, liver function, serum protein electrophoresis, rheumatoid factor, complete blood count, antinuclear antibodies) can confirm or rule out most of the differential diagnoses. Pertinent diagnostic and imaging studies can be helpful in certain circumstances, e.g., colonoscopy in suspected inflammatory bowel disease.
Untreated chronic inflammation generally carries a poor prognosis. Disease-specific morbidity and mortality are dependent on the causative mechanistic process leading to chronic inflammation.
Although chronic inflammation progresses silently, it is the cause of most chronic diseases and presents a major threat to the health and longevity of individuals. Inflammation is considered a major contributor to several diseases.
Chronic inflammation can have a deleterious effect on the body and is a key factor causing almost all chronic degenerative diseases. The following are some of the most effective ways to prevent chronic inflammation.
There are several chronic inflammatory disorders with no cure. Most are managed with symptomatic therapy. An interprofessional team including primary care physicians, nurses, physical therapists, dieticians, and specialists should be involved in the management of the underlying etiology, as well as prevention of complications of chronic inflammation. Patient education is the key with emphasis on diet and lifestyle modification including weight loss, regular exercises, smoking cessation, healthy diet, and good sleep hygiene. Unfortunately in some cases, life long anti-inflammatory medications may be needed to control chronic inflammation.
|||Michels da Silva D,Langer H,Graf T, Inflammatory and Molecular Pathways in Heart Failure-Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis. International journal of molecular sciences. 2019 May 10; [PubMed PMID: 31083399]|
|||Zhang X,Wu X,Hu Q,Wu J,Wang G,Hong Z,Ren J, Mitochondrial DNA in liver inflammation and oxidative stress. Life sciences. 2019 May 9; [PubMed PMID: 31078546]|
|||Fritsch J,Abreu MT, The Microbiota and the Immune Response: What Is the Chicken and What Is the Egg? Gastrointestinal endoscopy clinics of North America. 2019 Jul; [PubMed PMID: 31078242]|
|||Barcelos IP,Troxell RM,Graves JS, Mitochondrial Dysfunction and Multiple Sclerosis. Biology. 2019 May 11; [PubMed PMID: 31083577]|
|||Tsai DH,Riediker M,Berchet A,Paccaud F,Waeber G,Vollenweider P,Bochud M, Effects of short- and long-term exposures to particulate matter on inflammatory marker levels in the general population. Environmental science and pollution research international. 2019 May 12; [PubMed PMID: 31079306]|
|||Deepak P,Axelrad JE,Ananthakrishnan AN, The Role of the Radiologist in Determining Disease Severity in Inflammatory Bowel Diseases. Gastrointestinal endoscopy clinics of North America. 2019 Jul; [PubMed PMID: 31078247]|
|||Yousuf A,Ibrahim W,Greening NJ,Brightling CE, T2 Biologics for Chronic Obstructive Pulmonary Disease. The journal of allergy and clinical immunology. In practice. 2019 May - Jun; [PubMed PMID: 31076058]|
|||Milenkovic VM,Stanton EH,Nothdurfter C,Rupprecht R,Wetzel CH, The Role of Chemokines in the Pathophysiology of Major Depressive Disorder. International journal of molecular sciences. 2019 May 9; [PubMed PMID: 31075818]|
|||Cutolo M,Soldano S,Smith V, Pathophysiology of systemic sclerosis: current understanding and new insights. Expert review of clinical immunology. 2019 May 3; [PubMed PMID: 31046487]|
|||Needham EJ,Helmy A,Zanier ER,Jones JL,Coles AJ,Menon DK, The immunological response to traumatic brain injury. Journal of neuroimmunology. 2019 Apr 11; [PubMed PMID: 31005712]|