Inflammation

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Latest Edit: Iva 2012-3-31 (EDT)

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Inflammation is a physiological process that has been described since ancient times as a response to infection or injury characterized by cardinal symptoms of redness (rubor) and swelling (tumor) with heat (calore) and pain (dolore) and possibly the loss of function (functio laesa). The steps involved in the development of the inflammatory process are well understood as part of the normal immune response of host defense and tissue repair.

Contents

Role of Inflammation

  • If the inflammatory process is carefully controlled normal healing can occur.
  • If the inflammatory response is more vigorous than necessary or persists for an extended period of time it can contribute to disease.
  • Non-resolving inflammation is a major contributing factor to most chronic diseases.[1]
  • It is now evident that not all levels and types of inflammation are harmful but that some are necessary to adapt to stress, restore homeostasis or to retain the optimal functioning of an organ.[2] For example, in the intestines a certain constitutive level of activity of NF-kB and therefore, production of inflammatory signals is needed to support the turnover of epithelial cells needed during normal wear and tear as well as maintain the integrity of the intestinal barrier.[3], [4] This is good example of physiological, rather than pathological, inflammation.[5]

Contributing Factors

Many of the major contributing factors to inflammation also are well known including:

  • transcription factors such as nuclear factor kappa beta (NF-kB)[6]
  • proinflammatory cytokines including interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF)
  • cycloxygenase enzymes (COX)
  • leukotrienes and
  • prostaglandins.[7], [8]

Current evidence suggests that although these and other commonly described signalling molecules do play important roles in the inflammatory process it is much more complex with many more molecules orchestrating the entire process in an interrelated network.[7] One particular recent development is the discovery of the inflammasome, a tightly regulated intracellular multiprotein complex of the innate immune system at the hub of the signalling pathways of different inflammatory diseases including obesity-induced inflammation, insulin resistance and autoimmunity.[9], [10]

Inflammation Symptoms

  • Warmth and redness result from dilation of the small blood vessels in the injured area and increased local blood flow.
  • Swelling occurs due to the increased permeability of the blood vessels during inflammation. Protein rich exudates escapes from the blood plasma to the damaged tissues causing swelling.
  • Pain is a result of chemical substances such as serotonin or from tension of tissue over the inflamed area.

Inflammation Triggers

  • Infection
  • Trauma
  • Danger or damage signals (this is termed sterile inflammation).[11]
  • Carefully processed and released fragments of the extracellular matrix (such as the proteoglycan fragment biglycan),[12], [13] neurological pathways involving the brain (for example, the cholinergic anti-inflammatory pathway between the brain and gastrointestinal tract)[14], [15] and even cellular stress within certain tissues (resulting in an uncoupling protein response in the endoplasmic reticulum) such as that found in obesity, insulin resistance, cardiovascular and inflammatory bowel diseases.[16], [17]
  • Chronic inflammation in certain tissues is not just a local phenomenon but also triggers the release of signals that affect the brain to potentially cause the associated fatigue, anxiety and depression.[18]

Conditions

There are many conditions that are associated with increased inflammation including:

Lab Tests

Other considerations

  • During the initial phases of inflammation molecules including lipoxins, resolvins, maresins are produced from the metabolism of omega-3 and omega 6 fatty acids in various contributing cells. These molecules are actively released to function as termination signals or help promote timely resolution of inflammation.[20], [21] If these molecules are blocked, as is commonly the case with most mainstream anti-inflammatory drugs, healing is compromised with an increased likelihood of extended periods of wound healing, development of scar tissue and maintenance of pain.[22] This current understanding of the importance of these inflammation resolving molecules in normal healing has triggered the development of what is sometimes termed the post-aspirin era of inflammation with current searching for medications that promote resolution of inflammation or are at least non-toxic to the synthesis and secretion of the molecules involved in the physiological resolution of inflammation.
  • Inflammation must no longer be viewed as something negative that needs to be quickly suppressed but a process that is an integral part of the normal healing response and therefore, must be supported. Natural medicines including plant-based extracts and fish oils have been shown to work effectively within this modern view of inflammation to assist with modulating the potentially damaging components of the inflammatory process without interfering with the natural resolution pathways.

References

  1. Nathan C, Ding A (2010) Non-resolving inflammation. Cell;140:871-882.
  2. Medzhitov R (2008) Origin and physiological roles of inflammation. Nature;454:428-435.
  3. Guma M, Stepniak D et al. (2011) Constitutive intestinal NF-{kappa}B does not trigger destructive inflammation unless accompanied by MAPK activation. J Exp Med;208(9):1889-1900.
  4. Spehlmann ME, Eckman L (2009) Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol;25(2):92-94.
  5. Fiocchi C (2008) What is "physiological" intestinal inflammation and how does it differ from "pathological" inflammation? Inflamm Bowel Dis;14 Suppl 2:S77-8.
  6. Barnes BJ, Karin M (1997) Nuclear Factor k-B—A pivotal transcription factor in chronic inflammatory disease. N Eng J Med;336(15):1066-1071.
  7. 7.0 7.1 Dinarello CA (2000) Proinflammatory cytokines. Chest;118:503-508.
  8. Calvano SE, Xiao W et al. (2005) A network-based analysis of systematic inflammation in humans. Nature;437:1032-1037.
  9. Lukens JR, Dixit VD, Kannegati TD (2011) Inflammasome activation in Obesity-related Inflammatory Diseases and Autoimmunity. Discov Med;12(62):65-74.
  10. Vandanmagsar B, Youm Y-H et al. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Medicine;17:179-188.
  11. Chen GY, Nunez G. (2010) Sterile inflammation: sensing and reacting to damage. Nature Reviews Immunol;(10):826-837.
  12. Moreth K, Brodbeck R et al. (2010) The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis. J Clin Invest;120(12):4251-72.
  13. Bird L (2011) Inflammation: Directions from the matrix. Nature Rev Immunol;11(1):6.
  14. Tracer KJ (2007) Physiology and immunology of the cholinergic anti-inflammatory pathway. J Clin Invest;117(2):289-296.
  15. Gallowitsch-Puerta M, Pavlov VA (2007) Neuro-immune interactions via the cholinergi anti-inflammatory pathway. Life Sci;80(24-25):2325-2329.
  16. Rath E, Haller D (2011) Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies. Eur J Nutr;50(4):219-233.
  17. Hummastic S, Hotamisligil GS (2010) Endoplasmic reticulum stress and inflammation in obesity and diabetes. Cir Res;107(5):579-591.
  18. Dantzer R, O’Connor JC et al. (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Immunol;9(1):46-56.
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  20. Serhan CN, Chiang N, van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution mediators. Nat Rev Immunol;8(5):349-361.
  21. Serhan CN (2011) The resolution of inflammation: the devil in the flask and in the details. FASEB J.;25(5):1441-1448.
  22. Kohli P, Levy BD (2009) Review: Resolvin and protectins: mediating solutions to inflammation. Br J Pharmacol;158:960-971.
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