Anti-inflammatory is the property of a substance or treatment that reduces

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

or swelling. Anti-inflammatory

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...

s, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid u ...

, which affect the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

to block pain signaling to the brain.

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration o ...

s (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deri ...

, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the inflammation and resulting pain. Some common examples of NSAIDs are

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ar ...

, and naproxen. The newer specific COX-inhibitors are not classified together with the traditional NSAIDs, even though they presumably share the same mode of action. On the other hand, there are

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

s that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is

paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferio ...

(known as

acetaminophen Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

in the U.S). Contrary to NSAIDs, which reduce pain and inflammation by inhibiting COX enzymes, paracetamol has—as early as 2006—been shown to block the reuptake of endocannabinoids, which only reduces pain, likely explaining why it has minimal effect on inflammation; paracetamol is sometimes combined with an NSAID (in place of an opioid) in clinical practice to enhance the pain relief of the NSAID, while still receiving the injury/disease modulating effect of NSAID-induced inflammation reduction (which is not received from opioid/paracetamol combinations).

Side effects

Long-term use of NSAIDs can cause gastric erosions, which can become

stomach ulcers Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...

and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of GI bleeding caused by the use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk increases almost twentyfold for those over 75. Other dangers of NSAIDs are exacerbating asthma and causing kidney damage. Apart from aspirin, prescription and over-the-counter NSAIDs also increase the risk of

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

and

stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...

Antileukotrienes

Antileukotrienes are anti-inflammatory agents which function as leukotriene-related

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a ...

s ( arachidonate 5-lipoxygenase) or leukotriene

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

s (

cysteinyl leukotriene receptor The cysteinyl leukotriene receptors (CysLTRs) include the following two receptors: * Cysteinyl leukotriene receptor 1 (CysLTR1) * Cysteinyl leukotriene receptor 2 (CysLTR2) The recently elucidated CysLTE, represented by GPR99/OXGR1, may const ...

s), and consequently oppose the function of these inflammatory mediators. Although they are not used for

benefits, they are widely utilized in the treatment of diseases related to inflammation of the lungs (e.g.,

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

), as well as sinus inflammation in

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...

. They are also being investigated for use in diseases and injuries involving inflammation of the brain (e.g.,

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

Immune selective anti-inflammatory derivatives (ImSAIDs)

ImSAIDs are a class of

peptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

being developed by IMULAN BioTherapeutics, LLC, which were discovered to have diverse biological properties, including anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory cells, which are immune cells responsible for amplifying the inflammatory response. The ImSAIDs represent a new category of anti-inflammatory and are unrelated to

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

hormones or nonsteroidal anti-inflammatories. The ImSAIDs were discovered by scientists evaluating biological properties of the

submandibular gland The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimul ...

and

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can ...

. Early work in this area demonstrated that the submandibular gland released a host of factors that regulate systemic inflammatory responses and modulate systemic immune and inflammatory reactions. It is now well accepted that the immune, nervous, and

endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neur ...

systems communicate and interact to control and modulate

and tissue repair. One of the neuroendocrine pathways, when activated, results in the release of immune-regulating peptides from the submandibular gland upon neuronal stimulation from sympathetic nerves. This pathway or communication is referred to as the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the systemic control of inflammation. Early work in identifying factors that played a role in the CST-SMG axis led to the discovery of a seven

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

, called the submandibular gland peptide-T. SGP-T was demonstrated to have

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

and thermoregulatory properties related to endotoxin exposure. SGP-T, an isolate of the submandibular gland, demonstrated its immunoregulatory properties and potential role in modulating the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently was shown to play an important role in the control of inflammation. One SGP-T derivative is a three-amino acid sequence shown to be a potent anti-inflammatory

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and b ...

with systemic effects. This three-amino acid peptide is

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amin ...

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

(FEG) and its D-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

ic form (feG) have become the foundation for the ImSAID category. Cellular Effects of feG: The cellular effects of the ImSAIDs are characterized in a number of publications. feG and related peptides are known to modulate leukocyte (white blood cells) activity by influencing cell surface receptors to inhibit excessive activation and tissue infiltration. One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known to alter leukocyte adhesion involving actions on αMβ2

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle ...

, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils. feG has also been shown to decrease circulating

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

and eosinophil accumulation, decrease intracellular

oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

activity, and reduce the expression of CD49d after antigen exposure.

Bioactive compounds

Many

bioactive compound A bioactive compound is a compound that has an effect on a living organism, tissue or cell, usually demonstrated by basic research in vitro or in vivo in the laboratory. While dietary nutrients are essential to life, bioactive compounds have not ...

s showed anti-inflammatory activities on albino rat. In April 2014, plumericin from the Amazonian plant ''Himatanthus sucuuba'' has been described as a potent anti-inflammatory agent ''in vitro'' and ''in vivo''. Essential oils and extracts from some condiment plants have also been reported with anti-inflammatory activities—due to the presence of bioactive compounds such as

eugenol Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, bas ...

, eucalyptol, menthone, and

menthol Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature ...

Long-term effects

Anti-inflammatory treatment trials for existing

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As ...

have typically shown little to no effect on halting or reversing the disease. Research and clinical trials continue. Two studies from 2012 and 2013 found that regular use of

for over ten years is associated with an increase in the risk of

macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, so ...

Ice treatment

Applying ice, or even cool water, to a tissue injury has an anti-inflammatory effect, and is often suggested as an injury treatment and pain management technique for athletes. One common approach is rest, ice, compression and elevation. Cool temperatures inhibit local blood circulation, which reduces swelling in the injured tissue and relieves pain.

Health supplements

In addition to medical drugs, some herbs and health supplements may have anti-inflammatory qualities:

bromelain Bromelain is an enzyme extract derived from the stems of pineapples, although it exists in all parts of the fresh pineapple. The extract has a history of folk medicine use. As an ingredient, it is used in cosmetics, as a topical medication, and ...

from pineapples ('' Ananas comosus'').

Cannabichromene Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, is an anti-inflammatory which may contribute to the pain-killing effect of cannabis. It is one of the hundreds of cannabinoids found i ...

, a cannabinoid, also has anti-inflammatory effect. Honokiol from ''

Magnolia ''Magnolia'' is a large genus of about 210 to 340The number of species in the genus ''Magnolia'' depends on the taxonomic view that one takes up. Recent molecular and morphological research shows that former genera ''Talauma'', ''Dugandiodendr ...

'' inhibits platelet aggregation, and works as an inverse agonist at the CB2 receptor. Black seed (''

Nigella sativa ''Nigella sativa'' (black caraway, also known as black cumin, nigella, kalonji or siyahdaneh) is an annual flowering plant in the family Ranunculaceae, native to eastern Europe (Bulgaria and Romania) and Western Asia (Cyprus, Turkey, Iran and I ...

'') has shown anti-inflammatory effect due to its high

thymoquinone Thymoquinone is a phytochemical compound found in the plant ''Nigella sativa''. It is also found in select cultivated ''Monarda fistulosa ''Monarda fistulosa'', the wild bergamot or bee balm,St. John's wort's chief constituent, hyperforin, has been found to be a potent COX-1 and 5-LO inhibitor, with anti-inflammatory effect several fold that of aspirin.

Coal tar Coal tar is a thick dark liquid which is a by-product of the production of coke and coal gas from coal. It is a type of creosote. It has both medical and industrial uses. Medicinally it is a topical medication applied to skin to treat pso ...

has been used for centuries for its anti-inflammatory and analgesic effects. Oral administration for central effects is now rare as coal tar also contains a range of dangerous and

carcinogenic A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...

compounds, and does not allow for the administration of standardized doses, although some doctors readily utilize coal tar preparations for topical administration (e.g., Denorex, Psoriasin) in the treatment of skin conditions such as

eczema Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved c ...

and

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin ( dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens over tim ...

. Many modern analgesics and anti-inflammatory agents (such as paracetamol and its predecessor

phenacetin Phenacetin (acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn ...

) are derived from compounds which were originally discovered during studies to elucidate the chemicals responsible for the tars reputed health benefits.

Dietary patterns

Nutrition is linked to oxidative stress and inflammation. Foods that promote oxidative stress can also promote inflammation, while antioxidative foods may help bringing inflammation levels down. Other pathways may include the link between nutrition and hormones that effect inflammation. Observational studies show positive effects of low glycemic carbohydrates, whole grains, nuts, seeds, fruits, vegetables, fish and tea. Interventional studies show no effect with whole grains but with tea, vegetables and fruits. There is concern about

saturated fat A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branche ...

, which is mainly found in animal products, can promote inflammation. Epidemiological studies show that a

vegetarian Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter. Vegetariani ...

or mediterranean diet is associated with lower inflammation levels. A 2022 meta study found that plant-based diets such as a vegan, vegetarian, or mediterranean diet or the DASH diet are associated with lower inflammation levels and lower oxidative stress. By contrast a Western pattern diet based on white flour, red and processed meat was associated with higher inflammation levels and more oxidative stress.

Measurement of dietary inflammation

The Dietary Inflammatory Index (DII) is a score (number) that describes the potential of diet to modulate systemic inflammation within the body. The creation of the DII is attributed to scientists led by James R. Hébert at the Statewide South Carolina Cancer Prevention and Control Program at the University of South Carolina. It is based on the review and scoring of 1943 peer-reviewed scientific articles on diet and six inflammatory biomarkers published through 2010. According to Clarivate Web of Science, as of 23 November a total of 480 peer-reviewed scientific articles, including 39 meta-analyses, have been published based on the DII and these have been cited a total of 7545 times.

Exercise

Developing research has demonstrated that many of the benefits of exercise are mediated through the role of skeletal muscle as an endocrine organ. That is, contracting muscles release multiple substances known as

myokine A myokine is one of several hundred cytokines or other small proteins (~5–20 kDa) and proteoglycan peptides that are produced and released by skeletal muscle cells (muscle fibers) in response to muscular contractions. They have autocrine, paracr ...

s which promote the growth of new tissue, tissue repair, and various anti-inflammatory functions, which in turn reduce the risk of developing various inflammatory diseases.

Interactions with NSAIDs

Patients on NSAIDs should seek to avoid excessive consumption of omega-6 containing foods. Although many such foods contain the anti-inflammatory omega-3 as well, low doses of omega-6 interfere with omega-3's ability to reduce inflammation, while higher doses are capable of completely inhibiting the effects of most currently-used anti-inflammatory agents ( cyclooxygenase 1 inhibitors, cyclooxygenase 2 inhibitors, and antileukotrienes). The concomitant use of NSAIDs with

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

and/or

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

products significantly increases the already elevated risk of peptic ulcers during NSAID therapy. NSAID painkillers may interfere with and reduce the efficacy of SSRI antidepressants through inhibiting

TNFα Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

and IFNγ, both of which are cytokine derivatives.

References

{{DEFAULTSORT:Anti-Inflammatory *