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Anti-inflammatory

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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. These drugs reduce pain by inhibiting mechanisms of inflammation, as opposed to opioids, which affect the central nervous system to block pain.

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

Drugs

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Clinically approved

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Nonsteroidal anti-inflammatory drugs

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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 acetaminophen (paracetamol), 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

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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

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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] An example is montelukast and zileuton.

Monoclonal antibodies

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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

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Omega-3 fatty acids

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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

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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

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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-HT2A receptor agonists

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Serotonin 5-HT2A 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-HT2A receptor agonists with anti-inflammatory properties are under clinical investigation as possible treatments for inflammatory disorders.[20]

Tetracyclic antibiotics

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See also: Doxycycline § Anti-inflammatory agent

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]

Statins

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Statins like atorvastatin and simvastatin are used to treat inflammatory conditions like rheumatoid arthritis and chronic kidney disease.[24][25][26] Statins may be useful for treating other inflammatory conditions, like uveitis,[26] depression,[27][28] and possibly neuropsychiatric disorders.[29][30] However, higher-quality evidence of statins for treatment of neuropsychiatric and other conditions is still needed.[31]

References

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  1. ^ a b c Ghlichloo I, Gerriets V (1 May 2023). "Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)". StatPearls, US National Library of Medicine. Retrieved 25 May 2025.
  2. ^ Knights KM, Mangoni AA, Miners JO (November 2010). "Defining the COX inhibitor selectivity of NSAIDs: implications for understanding toxicity". Expert Rev Clin Pharmacol. 3 (6): 769–76. doi:10.1586/ecp.10.120. PMID 22111779. S2CID 207209534.
  3. ^ Qureshi O, Dua A (28 February 2024). "COX inhibitors". StatPearls, US National Library of Medicine. Retrieved 25 May 2025.
  4. ^ a b Gerriets V, Anderson J, Patel P, Nappe TM (11 January 2024). "Acetaminophen". StatPearls, US National Library of Medicine. Retrieved 25 May 2025.
  5. ^ a b "Table 7". NSAIDs and adverse effects. Bandolier. Archived from the original on February 18, 2012. Retrieved December 20, 2012.
  6. ^ Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M.; Egger, Matthias; Jüni, Peter (11 January 2011). "Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis". British Medical Journal. 342: c7086. doi:10.1136/bmj.c7086. PMC 3019238. PMID 21224324.
  7. ^ Ingawale DK, Mandlik SK (April 2020). "New insights into the novel anti-inflammatory mode of action of glucocorticoids". Immunopharmacol Immunotoxicol. 42 (2): 59–73. doi:10.1080/08923973.2020.1728765. PMID 32070175.
  8. ^ Escoter-Torres L, Caratti G, Mechtidou A, Tuckermann J, Uhlenhaut NH, Vettorazzi S (2019). "Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor". Front Immunol. 10: 1859. doi:10.3389/fimmu.2019.01859. PMC 6693390. PMID 31440248.
  9. ^ Dvorak J, Feddermann N, Grimm K (July 2006). "Glucocorticosteroids in football: use and misuse". British Journal of Sports Medicine. 40 (Suppl 1): i48–54. doi:10.1136/bjsm.2006.027599. PMC 2657490. PMID 16799104.
  10. ^ Scott JP, Peters-Golden M (September 2013). "Antileukotriene agents for the treatment of lung disease". Am. J. Respir. Crit. Care Med. 188 (5): 538–544. doi:10.1164/rccm.201301-0023PP. PMID 23822826.
  11. ^ Lai Y, Dong C (April 2016). "Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases". Int Immunol. 28 (4): 181–188. doi:10.1093/intimm/dxv063. PMC 4889878. PMID 26545932.
  12. ^ Li P, Zheng Y, Chen X (2017). "Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics". Front Pharmacol. 8: 460. doi:10.3389/fphar.2017.00460. PMC 5506195. PMID 28785220.
  13. ^ Yoo SM, Chung SH (April 2019). "Targets of monoclonal antibodies for immunological diseases". Arch Pharm Res. 42 (4): 293–304. doi:10.1007/s12272-018-1087-2. PMID 30426387.
  14. ^ a b c "Omega-3 Fatty Acids: Fact Sheet for Health Professionals". Office of Dietary Supplements, US National Institutes of Health. 17 December 2024. Retrieved 25 May 2025.
  15. ^ Calder PC (October 2017). "Omega-3 fatty acids and inflammatory processes: from molecules to man". Biochem Soc Trans. 45 (5): 1105–1115. doi:10.1042/BST20160474. PMID 28900017.
  16. ^ Santus P, Signorello JC, Danzo F, Lazzaroni G, Saad M, Radovanovic D (July 2024). "Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective". J Clin Med. 13 (14): 4127. doi:10.3390/jcm13144127. PMC 11278452. PMID 39064168.
  17. ^ a b Cho JH, Bhutani S, Kim CH, Irwin MR (March 2021). "Anti-inflammatory effects of melatonin: A systematic review and meta-analysis of clinical trials". Brain Behav Immun. 93: 245–253. doi:10.1016/j.bbi.2021.01.034. PMC 7979486. PMID 33581247.
  18. ^ Nichols DE, Johnson MW, Nichols CD (February 2017). "Psychedelics as Medicines: An Emerging New Paradigm". Clin Pharmacol Ther. 101 (2): 209–219. doi:10.1002/cpt.557. PMID 28019026.
  19. ^ a b Nichols CD (November 2022). "Psychedelics as potent anti-inflammatory therapeutics". Neuropharmacology. 219: 109232. doi:10.1016/j.neuropharm.2022.109232. PMID 36007854.
  20. ^ Kozlowska U, Nichols C, Wiatr K, Figiel M (July 2022). "From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders". J Neurochem. 162 (1): 89–108. doi:10.1111/jnc.15509. PMID 34519052.
  21. ^ Park CS, Kim SH, Lee CK (December 2020). "Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines". Immune Netw. 20 (6): e47. doi:10.4110/in.2020.20.e47. PMC 7779869. PMID 33425432.
  22. ^ Singh S, Khanna D, Kalra S (2021). "Minocycline and Doxycycline: More Than Antibiotics". Curr Mol Pharmacol. 14 (6): 1046–1065. doi:10.2174/1874467214666210210122628. PMID 33568043.
  23. ^ Al Jumaili W, Vora D, Trivedi C, Jain S (September 2023). "Role of Minocycline as an Adjunct Neuroinflammatory Modulator in Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials". Prim Care Companion CNS Disord. 25 (5). doi:10.4088/PCC.22r03467. PMID 37713730. Results: Minocycline as an adjunct immunomodulator shows inconsistent benefit in TRD. Minocycline has some beneficial effect on depression scale scores and inflammatory markers in TRD patients with inflammatory disequilibrium (C-reactive protein elevation exceeds 3 mg/L). However, minocycline showed an inconclusive effect in TRD with no clear immunologic dysregulation.
  24. ^ Li GM, Zhao J, Li B, Zhang XF, Ma JX, Ma XL, Liu J (March 2018). "The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A systemic review and meta-analysis of 15 randomized controlled trials". Autoimmun Rev. 17 (3): 215–225. doi:10.1016/j.autrev.2017.10.013. PMID 29353098.
  25. ^ Wang J, Chen Z, Qiu Y, Wu L, Wang H, Wu L, Zhao L, Xie D (2022). "Statins Have an Anti-Inflammation in CKD Patients: A Meta-Analysis of Randomized Trials". Biomed Res Int. 2022: 4842699. doi:10.1155/2022/4842699. PMC 9617709. PMID 36317110.
  26. ^ a b Gilbert R, Al-Janabi A, Tomkins-Netzer O, Lightman S (2017). "Statins as anti-inflammatory agents: A potential therapeutic role in sight-threatening non-infectious uveitis". Porto Biomed J. 2 (2): 33–39. doi:10.1016/j.pbj.2017.01.006. PMC 6806973. PMID 32258583. In addition to the known lipid-lowering effects, statins are now widely accepted to have anti-inflammatory and immunomodulatory effects. Adjunctive use of statins has proven beneficial in the context of a wide range of inflammatory diseases, including rheumatoid arthritis.
  27. ^ De Giorgi R, De Crescenzo F, Rizzo Pesci N, Martens M, Howard W, Cowen PJ, Harmer CJ (2021). "Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials". PLOS ONE. 16 (3): e0249409. Bibcode:2021PLoSO..1649409D. doi:10.1371/journal.pone.0249409. PMC 8009386. PMID 33784356.
  28. ^ Bai S, Guo W, Feng Y, Deng H, Li G, Nie H, Guo G, Yu H, Ma Y, Wang J, Chen S, Jing J, Yang J, Tang Y, Tang Z (January 2020). "Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials". J Neurol Neurosurg Psychiatry. 91 (1): 21–32. doi:10.1136/jnnp-2019-320912. PMID 31658959.
  29. ^ Avan R, Sahebnasagh A, Hashemi J, Monajati M, Faramarzi F, Henney NC, Montecucco F, Jamialahmadi T, Sahebkar A (December 2021). "Update on Statin Treatment in Patients with Neuropsychiatric Disorders". Life (Basel). 11 (12): 1365. Bibcode:2021Life...11.1365A. doi:10.3390/life11121365. PMC 8703562. PMID 34947895.
  30. ^ Fitton R, Sweetman J, Heseltine-Carp W, van der Feltz-Cornelis C (December 2022). "Anti-inflammatory medications for the treatment of mental disorders: A scoping review". Brain Behav Immun Health. 26: 100518. doi:10.1016/j.bbih.2022.100518. PMC 9547233. PMID 36217374.
  31. ^ Köhler-Forsberg O, Otte C, Gold SM, Østergaard SD (November 2020). "Statins in the treatment of depression: Hype or hope?". Pharmacol Ther. 215: 107625. doi:10.1016/j.pharmthera.2020.107625. PMID 32652185.
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