Anti-inflammatory

Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics.^{[not verified in body]} These drugs reduce pain by inhibiting mechanisms of inflammation, as opposed to opioids, which affect the central nervous system to block pain.^{[not verified in body]}

Common anti-inflammatory drugs include nonsteroidal anti-inflammatory drugs (NSAIDs),^[1] corticosteroids, antileukotrienes, and monoclonal antibodies.

Drugs

Clinically approved

Nonsteroidal anti-inflammatory drugs

Main article: Nonsteroidal anti-inflammatory drug

NSAIDs alleviate pain by counteracting the cyclooxygenase (COX) enzyme involved in pain mechanisms.^[1][2]

Some common examples of NSAIDs are aspirin, ibuprofen, and naproxen.^[1] Selective COX-2 inhibitors, such as celecoxib, block the enzymatic conversion of arachidonic acid into prostaglandin, inhibiting inflammation and pain.^[3]

Analgesics commonly associated with anti-inflammatory drugs, such as paracetamol (acetaminophen), have no peripheral anti-inflammatory effects.^[4] High, short-term doses of NSAIDs may become toxic, causing gastric erosions, stomach ulcers, internal bleeding, hepatotoxicity, or kidney disease.^[4]

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.^[5] The risk increases almost twentyfold for those over 75.^[5] Apart from aspirin, frequent or high doses of prescription and over-the-counter NSAIDs may increase the risk of heart attack and stroke.^[6]

Corticosteroids

Corticosteroids, specifically glucocorticoids or glucocorticoid receptor agonists, are powerful anti-inflammatory agents, but they are also powerful immunosuppressants and are associated with various toxicities, which constrain their use.^[7][8]

Antileukotrienes

Antileukotrienes are anti-inflammatory agents which function as leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors), and consequently oppose the function of these inflammatory mediators. Although they are not used for analgesic benefits, they are widely used to treat diseases related to inflammation of the lungs, such as asthma and COPD, as well as sinus inflammation in allergic rhinitis.^[9][10] Examples include montelukast and zileuton.

Monoclonal antibodies

Monoclonal antibodies, for instance against pro-inflammatory cytokines like interleukin-6 (anti-interleukin-6) and tumor necrosis factor α (TNFα) (TNF inhibitors), are approved and used in the treatment autoimmune diseases and other inflammatory conditions.^[11][12][13]

Investigational and off-label

Omega-3 fatty acids

Omega-3 fatty acids may have anti-inflammatory effects, although clinical studies show that possible effects have been inconsistent, requiring further research.^[14] A 2017 review indicated that omega-3 fatty acids may benefit rheumatoid arthritis,^[15] although another analysis indicated no consistent effect.^[14] There is no good evidence that use of omega-3 fatty acids provides relief in retinal inflammation or in dry eye syndrome.^[14]

N-Acetylcysteine

N-Acetylcysteine (NAC) has been found to possess anti-inflammatory effects and has been clinically studied in the treatment of conditions involving inflammation.^[16]

Melatonin

A 2021 review reported that melatonin has anti-inflammatory effects.^[17] Found to reduce levels of several pro-inflammatory cytokines, it remains under preliminary research for its potential to treat inflammation.^[17]

Serotonin 5-HT_2A receptor agonists

Serotonin 5-HT_2A receptor agonists, including serotonergic psychedelics, are under preliminary research as possible anti-inflammatory agents.^[18][19] The anti-inflammatory effects of some psychedelics, like DOI and psilocybin, have been found to occur at much lower doses than those at which they produce their hallucinogenic effects.^[19] Serotonin 5-HT_2A receptor agonists with anti-inflammatory properties are under clinical investigation as possible treatments for inflammatory disorders.^[20]

Tetracyclic antibiotics

See also: Doxycycline § Anti-inflammatory agent, and Minocycline § Research

The tetracycline antibiotics minocycline and doxycycline have been found to have anti-inflammatory and immunomodulatory effects.^[21][22] Minocycline has been found to have some clinical benefit in people with treatment-resistant depression with inflammation but not in those without inflammation.^[23]

Macrolide antibiotics

See also: Azithromycin § Airway diseases, and Azithromycin § Research

The macrolide antibiotic azithromycin is known to have anti-inflammatory and immunomodulatory properties.^[24] It is said to be established and effective for certain inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD).^{[24][25][26][27]} Azithromycin is also being assessed for potential treatment of other chronic inflammatory disorders.^[28][29]

Statins

Statins like atorvastatin and simvastatin are used to treat inflammatory conditions like rheumatoid arthritis and chronic kidney disease.^[30][31][32] Statins may be useful for treating other inflammatory conditions, like uveitis,^[32] depression,^[33][34] and possibly neuropsychiatric disorders.^[35][36] However, higher-quality evidence of statins for treatment of neuropsychiatric and other conditions is still needed.^[37]

Curcumin

Curcumin, a curcuminoid and prominent active constituent of turmeric, has shown anti-inflammatory activity in preclinical research and has been of interest for the potential treatment of various inflammatory conditions.^[38][39] A 2019 systematic review and meta-analysis found that curcumin or turmeric did not significantly decrease several circulating inflammatory markers in patients with various chronic inflammatory diseases.^[40] However, subsequent 2021 and 2023 systematic reviews and meta-analyses found that curcumin or turmeric was able to reduce various circulating inflammatory markers.^[41][42] A major problem of curcumin which has limited its potential application is very poor oral bioavailability.^{[43][44][45][46]}