Anti-inflammatory

Anti-inflammatory (or antiinflammatory) is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme.[1] On its own, COX enzyme synthesizes prostaglandins, 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, ibuprofen, 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 analgesics that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is paracetamol (known as acetaminophen or Tylenol in the U.S). As opposed 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,[2][3] 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).[4]

Side effects

Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers 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.[5] The risk increases almost twentyfold for those over 75.[5] Other dangers of NSAIDs are exacerbating asthma and causing kidney damage.[5] Apart from aspirin, prescription and over-the-counter NSAIDs also increase the risk of heart attack and stroke.[6]

Antileukotrienes
Main article: Antileukotriene

Antileukotrines 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 utilized in the treatment of diseases related to inflammation of the lungs such as asthma and COPD as well as sinus inflammation in allergic rhinitis.[7][8] They are also being investigated for use in diseases and injuries involving inflammation of the brain (ex. Parkinsons disease).[9][10]

Immune selective anti-inflammatory derivatives (ImSAIDs)

ImSAIDs are a class of peptides 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.[11][12] The ImSAIDs represent a new category of anti-inflammatory and are unrelated to steroid hormones or nonsteroidal anti-inflammatories.

The ImSAIDs were discovered by scientists evaluating biological properties of the submandibular gland and saliva. 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 systems communicate and interact to control and modulate inflammation 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.[13]

Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acid peptide, called the submandibular gland peptide-T. SGP-T was demonstrated to have biological activity and thermoregulatory properties related to endotoxin exposure.[14] 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 with systemic effects. This three-amino acid peptide is phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG) have become the foundation for the ImSAID category.[15] 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, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils.[16] feG has also been shown to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular oxidative activity, and reduce the expression of CD49d after antigen exposure.[17][18][19]

Bioactive compounds

Many bioactive compounds showed anti-inflammatory activities on albino rat. More recently plumericin from the Amazonian plant Himatanthus sucuuba has been described as a potent anti-inflammatory agent in vitro and in vivo.[20] 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, eucalyptol, menthone, and menthol.[21]

Long-term effects

Anti-inflammatory treatment trials for existing Alzheimer's disease have typically shown little to no effect on halting or reversing the disease.[22][23] Research and clinical trials continue.[24] Two studies from 2012 and 2013 found regular use of aspirin for over ten years is associated with an increase in the risk of macular degeneration.[25][26]

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.

Health supplements

In addition to medical drugs, some herbs and health supplements may have anti-inflammatory qualities: bromelain from pineapples (Ananas comosus).[27] Cannabichromene, a cannabinoid, also has anti-inflammatory effect.[28] Honokiol from Magnolia inhibits platelet aggregation, and works as an inverse agonist at the CB2 receptor. Black seed (Nigella sativa) has shown anti-inflammatory effect due to its high thymoquinone content.[29] 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.[30]

Coal tar 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 compounds, and does not allow for the administration of standardized doses, although some doctors readily utilize coal tar preparations for topical administration (ex. Denorex, Psoriasin) in the treatment of skin conditions such as eczema and atopic dermatitis. Many modern analgesics and anti-inflammatory agents (ex. paracetamol, and its previously used predecessor phenacetin) are derived from compounds which were originally discovered during studies to elucidate the chemicals responsible for the tars reputed health benefits.[31][32]

Anti-inflammatory foods

Suggested diets to reduce inflammation include those rich in vegetables and low in simple carbohydrates, and fats such as saturated fats and trans fats.[33] Allegedly anti-inflammatory foods include most colorful fruits and vegetables, oily fish (which contain higher levels of omega-3 fatty acids), nuts, seeds, and certain spices, such as ginger, garlic and cayenne. Such a diet is virtually identical to almost all other diets claimed to be beneficial, with the recommended foods overlapping almost entirely with those recommended in the generic healthful diets nutritionists have known about for decades, suggesting the alleged benefits one feels on an anti-inflammation diet may have nothing to do with inflammation per se or from any anti-inflammatory effects of the foods, but rather come from having an over-all better diet.[34]

Omega-3 fatty acids have been shown to disrupt inflammation cell signaling pathways by binding to the GPR120 receptor.[35] This benefit however can be inhibited or even reversed if the ratio of Omega-6/Omega-3 is too high as Omega-6 serves as a precursor to inflammatory chemicals (prostaglandin and leukotriene eicosanoids) in the body.[36][37]

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 myokines 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.[38]

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).[39][40][41]

The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy.[42]

NSAID painkillers may interfere with and reduce the efficacy of SSRI antidepressants through inhibiting TNFα and IFNγ, both of which are cytokine derivatives.[43]

References
  1. 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.
  2. Ottani, Alessandra; Leone, Sheila; Sandrini, Maurizio; Ferrari, Anna; Bertolini, Alfio (February 15, 2006). "The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors". European Journal of Pharmacology. 531 (1–3): 280–281. doi:10.1016/j.ejphar.2005.12.015. hdl:11380/613413. PMID 16438952.
  3. Dani, Mélina; Guindon, Josée; Lambert, Chantal; Beaulieu, Pierre (November 14, 2007). "The local antinociceptive effects of paracetamol in neuropathic pain are mediated by cannabinoid receptors". European Journal of Pharmacology. 573 (1–3): 214–215. doi:10.1016/j.ejphar.2007.07.012. PMID 17651722.
  4. Merry AF, Gibbs RD, Edwards J, Ting GS, Frampton C, Davies E, Anderson BJ (January 2010). "Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial". British Journal of Anaesthesia. 104 (1): 80–8. doi:10.1093/bja/aep338. PMC 2791549. PMID 20007794.
  5. "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 (Clinical Research Ed.). 342: c7086. doi:10.1136/bmj.c7086. PMC 3019238. PMID 21224324.
  7. 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.
  8. 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.
  9. Hamzelou, Jessica (23 October 2015). "Old rat brains rejuvenated and new neurons grown by asthma drug". New Scientist. Retrieved 28 October 2015.
  10. Yirka, Bob. "Asthma drug found to rejuvenate older rat brains". medicalxpress.com. Retrieved 3 November 2015.
  11. Bao, F.; John, S.M.; Chen, Y.; Mathison, R.D.; Weaver, L.C. (2006). "The tripeptide phenylalanine-(d) glutamate-(d) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord". Neuroscience. 140 (3): 1011–1022. doi:10.1016/j.neuroscience.2006.02.061. PMID 16581192. S2CID 6450375.
  12. Mathison, Ronald D.; Befus, A. Dean; Davison, Joseph S.; Woodman, Richard C. (2003). "Modulation of neutrophil function by the tripeptide feG". BMC Immunology. 4 (3): 3. doi:10.1186/1471-2172-4-3. PMC 152650. PMID 12659660.
  13. Mathison, R.; Davison, J.S.; Befus, A.D. (November 1994). "Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors". Immunology Today. 15 (11): 527–532. doi:10.1016/0167-5699(94)90209-7. PMID 7802923.
  14. Mathison, Ronald D.; Malkinson, Terrance; Cooper, K.E.; Davison, J.S. (1997). "Submandibular glands: novel structures participating in thermoregulatory responses". Canadian Journal of Physiology and Pharmacology. 75 (5): 407–413. doi:10.1139/y97-077. PMID 9250374.
  15. Dery, R.E.; Mathison, R.; Davison, J.; Befus; A.D. (2001). "Inhibition of allergic inflammation by C-terminal peptides of the prohormone submandibular rat 1 (SMR-1)". International Archives of Allergy and Immunology. 124 (1–3): 201–024. doi:10.1159/000053710. PMID 11306968. S2CID 12810779.
  16. Mathison, Ronald D; Christie, Emily; Davison, Joseph S (1 January 2008). "The tripeptide feG inhibits leukocyte adhesion". Journal of Inflammation. 5 (1): 6. doi:10.1186/1476-9255-5-6. PMC 2408570. PMID 18492254.
  17. Dery, René E.; Ulanova, Marina; Puttagunta, Lakshmi; Stenton, Grant R.; et al. (2004). "Frontline: Inhibition of allergen-induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro-endocrine pathway". European Journal of Immunology. 34 (12): 3315–3325. doi:10.1002/eji.200425461. PMID 15549777. S2CID 24906971.
  18. Mathison, Ronald D.; Davison, Joseph S. (2006). "The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils". Journal of Inflammation. 3 (9): 9. doi:10.1186/1476-9255-3-9. PMC 1534017. PMID 16776845.
  19. Mathison, R.; Lo, P.; Tan, D.; Scott, B.; Davison, J. S. (2001). "The tripeptide feG reduces endotoxin-provoked perturbation of intestinal motility and inflammation". Neurogastroenterology & Motility. 13 (6): 599–603. doi:10.1046/j.1365-2982.2001.00294.x. PMID 11903921. S2CID 8620163.
  20. Fakhrudin, N.; Waltenberger, B.; Cabaravdic, M.; Atanasov, AG.; et al. (April 2014). "Identification of plumericin as a potent new inhibitor of the NF-κB pathway with anti-inflammatory activity in vitro and in vivo". Br J Pharmacol. 171 (7): 1676–86. doi:10.1111/bph.12558. PMC 3966748. PMID 24329519.
  21. Diniz do Nascimento, Lidiane; Moraes, Angelo Antônio Barbosa de; Costa, Kauê Santana da; Pereira Galúcio, João Marcos; Taube, Paulo Sérgio; Costa, Cristiane Maria Leal; Neves Cruz, Jorddy; de Aguiar Andrade, Eloisa Helena; Faria, Lênio José Guerreiro de (2020-07-01). "Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications". Biomolecules. 10 (7): 988. doi:10.3390/biom10070988. ISSN 2218-273X. PMID 32630297.
  22. "Anti-inflammatory drugs may not protect cognitive function". Harvard Mental Health Letter. 25 (2): 7. August 2008. PMID 18724438.
  23. Rogers, Joseph (2008). "The Inflammatory Response in Alzheimer's Disease". Journal of Periodontology. 79 (8 Supplement): 1535–1543. doi:10.1902/jop.2008.080171. PMID 18673008.
  24. Sano, M.; Grossman, H.; Van Dyk, K. (2008). "Preventing Alzheimer's disease: separating fact from fiction". CNS Drugs. 22 (11): 887–902. doi:10.2165/00023210-200822110-00001. PMID 18840031. S2CID 9444276.
  25. Liew, G.; Mitchell, P.; Wong, T. Y.; Rochtchina, E.; Wang, J. J. (2013). "The Association of Aspirin Use with Age-Related Macular Degeneration". JAMA Internal Medicine. 173 (4): 1–7. doi:10.1001/jamainternmed.2013.1583. PMID 23337937.
  26. Klein, B. E. K.; Howard, K. P.; Gangnon, R. E.; Dreyer, J. O.; Lee, K. E.; Klein, R. (2012). "Long-term Use of Aspirin and Age-Related Macular Degeneration". JAMA: The Journal of the American Medical Association. 308 (23): 2469–2478. doi:10.1001/jama.2012.65406. PMC 3630794. PMID 23288416.
  27. Akhtar, N.; Haqqi, T. M. (2012). "Current nutraceuticals in the management of osteoarthritis: A review". Therapeutic Advances in Musculoskeletal Disease. 4 (3): 181–207. doi:10.1177/1759720X11436238. PMC 3400101. PMID 22850529.
  28. Turner, Carlton, E.; Elsohly, Mahmoud A. (1981). "Biological activity of cannabichromene, its homologs and isomers" (PDF). Journal of Clinical Pharmacology. 21 (8–9 Supplement): 283S–291S. doi:10.1002/j.1552-4604.1981.tb02606.x. PMID 7298870. S2CID 35727143. Retrieved December 20, 2012.
  29. Alemi, M.; Sabouni, F.; Sanjarian, F.; Haghbeen, K.; Ansari, S. (2012). "Anti-inflammatory Effect of Seeds and Callus of Nigella sativa L. Extracts on Mix Glial Cells with Regard to Their Thymoquinone Content". AAPS PharmSciTech. 14 (1): 160–7. doi:10.1208/s12249-012-9899-8. PMC 3581679. PMID 23255199.
  30. Koeberle, Andreas; Rossi, Antonietta; Bauer, Julia; Dehm, Friederike; Verotta, Luisella; Northoff, Hinnak; Sautebin, Lidia; Werz, Oliver (2011-02-18). "Hyperforin, an Anti-Inflammatory Constituent from St. John's Wort, Inhibits Microsomal Prostaglandin E2 Synthase-1 and Suppresses Prostaglandin E2 Formation in vivo". Frontiers in Pharmacology. 2: 7. doi:10.3389/fphar.2011.00007. ISSN 1663-9812. PMC 3108608. PMID 21687502.
  31. Joshua A. Zeichner, MD (September 2010). "Use of Topical Coal Tar Foam for the Treatment of Psoriasis in Difficult-to-treat Areas". The Journal of Clinical and Aesthetic Dermatology. 3 (9): 37–40. PMC 2945847. PMID 20877524.
  32. van den Bogaard EH, Bergboer JG, Vonk-Bergers M, van Vlijmen-Willems IM, Hato SV, van der Valk PG, Schröder JM, Joosten I, Zeeuwen PL, Schalkwijk J (February 2013). "Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis". The Journal of Clinical Investigation. 123 (2): 917–27. doi:10.1172/JCI65642. PMC 3561798. PMID 23348739.
  33. "Dr. Weil's Anti-Inflammatory Food Pyramid". Dr Weil. Retrieved December 20, 2012.
  34. Katz, D. L.; Meller, S (March 2014). "Can We Say What Diet Is Best for Health?". Annual Review of Public Health. 35: 83–103. doi:10.1146/annurev-publhealth-032013-182351. Retrieved 16 November 2020.
  35. Willyard, Cassandra (September 2, 2010). "How Fish Oil Fights Inflammation". ScienceNOW. Retrieved December 20, 2012.
  36. Simopoulos, Artemis P. (2003). "Importance of the Ratio of Omega-6/Omega-3 Essential Fatty Acids: Evolutionary Aspects". In Simopoulos, Artemis P.; Cleland, Leslie G. (eds.). Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence. World Review of Nutrition and Dietetics. 92. pp. 1–22. doi:10.1159/000073788. ISBN 978-3-8055-7640-6. PMID 14579680.
  37. Wada, M.; Delong, C. J.; Hong, Y. H.; Rieke, C. J.; Song, I.; Sidhu, R. S.; Yuan, C.; Warnock, M.; et al. (2007). "Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products". Journal of Biological Chemistry. 282 (31): 22254–66. doi:10.1074/jbc.M703169200. PMID 17519235.
  38. Pedersen, BK. (Jul 2013). "Muscle as a secretory organ". Compr Physiol. 3 (3): 1337–62. doi:10.1002/cphy.c120033. ISBN 9780470650714. PMID 23897689.
  39. Cleland, Leslie G; James, Michael J; Proudman, Susanna M (2006). "Fish oil: what the prescriber needs to know". Arthritis Research & Therapy. 8 (1): 202. doi:10.1186/ar1876. PMC 1526555. PMID 16542466.
  40. Mickleborough, Timothy (2005). "Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma". Journal of Asthma. 42 (5): 305–14. doi:10.1081/JAS-62950. PMID 16036405. S2CID 8319697.
  41. K S Broughton; Johnson, CS; Pace, BK; Liebman, M; Kleppinger, KM (1997-04-01). "Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production". The American Journal of Clinical Nutrition. 65 (4): 1011–7. doi:10.1093/ajcn/65.4.1011. PMID 9094887.
  42. Agrawal N (June 1991). "Risk factors for gastrointestinal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs)". Journal of Family Practice. 32 (6): 619–24. PMID 2040888.
  43. Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P (May 2011). "Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans". Proc. Natl. Acad. Sci. U.S.A. 108 (22): 9262–7. Bibcode:2011PNAS..108.9262W. doi:10.1073/pnas.1104836108. PMC 3107316. PMID 21518864.
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