An overview of the inflammatory response

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     Inflammation is a pathological response that engages hundreds of mediators and different cells and tissue types. It can be initiated by any stimulus causing cell injury. Often the inflammation is a response to some sort of infection. In some cases, chemical or physical injury can also induce an inflammatory reaction. The goal of the inflammatory response is to remove the causative agent with minimal destruction to the body, and to repair the damage caused by the toxin. The duration of the inflammatory response is dependent on whether the causative agent has been eliminated. Acute inflammation is a relatively short process, lasting from minutes to a few days (Pahwa et al., 2020).

     If the acute inflammatory response is unable to remove the causative agent and restore the damaged tissue, this can lead to chronic inflammation. In which tissue destruction and repair happen while the inflammatory process continues. Chronic inflammation can also result from stimuli that initiate a low-grade asymptomatic response. Any injury that causes the cells to die will elicit an inflammatory response. The aim is to remove the debris of the dead cells and the source of the injury. Whatever type, phagocytic cells and blood proteins move to the area of infection. The response is dependent on both vasoactive and chemotactic messengers from the site of injury. The presence of chemotactic and vasoactive messengers causes the arrival of inflammatory cells to the injury site.

Acute inflammation works to remove any external invader and any necrotic cellular debris. To do this, phagocytes are attracted to the area by parts of the clotting components, through vasodilation and release of chemotactic messengers from the cells and blood plasma. The outcome of acute inflammation is dependent on the type and persistence of the injury. Also, the extent of the damage and how fast the specialised cells on the injury site increase in number. Tissue damage due to trauma, inversion of the microbes and other harmful compounds can induce an acute inflammatory response. An acute inflammatory response starts fast and symptoms may last anywhere from few days to three weeks.

  In chronic inflammation, the causative agent will stay in the body for a long time and continue to cause injury. This can last for months to several years and some chronic inflammatory illnesses are lifelong. The extent and effect of the chronic inflammatory response is dependent on the cause of the injury and the ability of the body to repair and overcome the damage. Chronic inflammation can result from; failure of eliminating the agent causing the acute inflammation such as infectious organisms like, mycobacterium tuberculosis, protozoa, fungi, and other parasites. An autoimmune disorder is also considered a chronic inflammatory response. Happens when the immune system recognises the normal components of the body as foreign and attacks the healthy tissue. As is the case with rheumatoid arthritis and systemic lupus erythematosus (Pahwa et al., 2020).


Inflammation 

Mast cells release histamine which causes vasodilation, increased plasma permeability of the vessels to phagocytic cells and fluid. This causes the injury site to be flooded with phagocytic cells, fluid and plasma proteins, this is called inflammatory exudate.

Signs of inflammation

  • Redness – dilation of the local blood vessels
  • Heat – from increased blood flow
  • Swelling – from the build-up of fluids and plasma proteins and loss of function due to tissue swelling.

The fluid and plasma proteins work by diluting any substances that may cause injury before they are drained into the hepatic system. Immunoglobulins and part of the complement cascade help to neutralise the microorganism. Other proteins like fibrinogens are converted into insoluble form, which forms a mesh at the injury site. The mesh plugs the wound and physically protecting it from infections. The first cells to arrive at the site are the neutrophils that phagocytose necrotic cellular debris, by releasing phagocytic enzymes from the lysosomes. When they have been used, the lysosomes enzymes die and become part of the debris.

The mast cells arrive at the area, monocytes are turned into macrophages when they are activated. Macrophages can regenerate their phagocytic enzymes, to aid in the digestion of the narcotic cellular debris. The lymphocytes may be part of the specific or non-specific immune mechanism or may have been freed from the tissue that was broken down by injury (Chen et al., 2017).


Repair

Repair is done through regeneration; this is where old tissue is replaced by the same type cells. And replacement by connective tissue. Regeneration of tissue can only happen when there are reserve cells at the site of injury that are able to go through mitosis. Usually there are three groups of cells:

  1. Labile cells – These are cells that generally proliferate throughout the lifespan replacing dead or dying cells that die through normal physiological means. For example, the epithelial at the surface of the skin.
  2. Stable cells – In some cases these cells regenerate, but usually don’t, because of their long survival time. For example, the cells of the glands, liver cells and the cells found in kidney collecting tubules.
  3. Permanent cells – These are neutrons and cardiac muscles cells, if a neuron dies, it is lost forever. But the axons can regenerate after an injury. Cardiac muscle cells die because of deprived oxygen, as seen in heart attacks. Repair depends on the existing framework being presented and if there is adequate blood supply.

 Angiogenesis is the formation of new blood vessels, that bud and sprout from pre-existing blood vessels. They form several branches which eventually grow and form capillary beds. They will subsequently form capillary beds and venules. Growth factors are usually involved during angiogenesis.


Mechanism of Healing 

Normal growth in cells is controlled by both growth factors and inhibitors. The most important are the factors that recruit quiescent cells to mitosis. These growth factors are called.

  1. Epidermal GF, EGF, EGR- 
  2. These play an important role in wound healing through stimulation of epidermal and dermal regeneration. EGF is important for mediating the differentiation of keratinocytes to an epithelial line and re-establishes an epithelial barrier.

PDGE –

  • These growth factors come from platelets but also from activated macrophages, endothelium, smooth muscles cells and tumour cells. It causes the migration and proliferation of fibroblasts, smooth muscle cells and the monocytes.

FGF –

  • These growth factors come from the fibroblasts, causes fibroblasts proliferation and new vascular growth. There are two types, we have the beta FGF that are found in most of the organs and secreted by the activated macrophages. The second is Alpha FGF which is in the neural tissue  (Bodnar, 2013).

 References

Darby, I. A., Laverdet, B., Bonté, F., & Desmoulière, A. (2014). Fibroblasts and myofibroblasts in wound healing. Clinical, cosmetic and investigational dermatology7, 301.

Shabbir, A., Cox, A., Rodriguez-Menocal, L., Salgado, M., & Badiavas, E. V. (2015). Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem cells and development24(14), 1635-1647.

Portou, M. J., Baker, D., Abraham, D., & Tsui, J. (2015). The innate immune system, toll-like receptors and dermal wound healing: a review. Vascular pharmacology71, 31-36.

Bodnar, R. J. (2013). Epidermal Growth Factor and Epidermal Growth Factor Receptor: The Yin and Yang in the Treatment of Cutaneous Wounds and Cancer. Advances in Wound Care, 2(1), 24–29. https://doi.org/10.1089/wound.2011.0326

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208

Pahwa, R., Goyal, A., Bansal, P., & Jialal, I. (2020). Chronic Inflammation. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK493173/

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