Inflammation is a natural response to the body’s immune system. It results from damage to body tissue, weather hit, punctured, or suffering from internal damage. Inflammation is most associated with the swelling occurs as a result. For this reason, inflammation is required for healing, (Vodovtz, 2010). When internal and/or external damage occurs, it provides cutaneous homeostasis. This is inflammation cell lineages and the cytokine network that work to repair the area and heal the wound. Despite its function, inflammation is typically observed as a negative consequence of bodily injury. Inflammation can predict scaring and how well a wound will heal. When a wound fails to heal and inflammation becomes chronic, increased damage may occur. This is seen in illness such as cancer, diabetes, Alzheimer’s disease and arthritis. Inflammation has both positive and negative results providing a unique relationship with health and healing. It is important analyze and gain clarity regarding the function of inflammation in the human body. By understanding the facts, studies, arguments and trends regarding inflammation, researchers can apply improved medical information and practices to damaged tissue ensuring positive results against increased damage and wound repair.
Inflammation is the result of a wound. It is defined by the presence of five major symptoms that are macroscopic in nature. A system of molecules and cells help mediate the process. When inflammation occur monocytes and macrophages are activated from the immune system. Of these, macrophages are most significant in the process of inflammation. Macrophages produce inflammation molecules to induce clotting and excrete free radicals to the injured area for growth. Additional cells and molecules are neutrophil. Neutrophil are white blood cells to by killing harmful agents caused by the wound. Lymphocytes B cells and T cells further help with the process by killing infected cells and attacking. Platelets also play a role in inflammation by helping to clot blood to open areas, (can der Meer, Maat, Bots, Bretler, Kiliaan, Hoffman & Witteman, 2002). Additional cells included in the process are mast cells, eosinophils, and endothelial cells. However, “we know little about the real biological significance of inflammation”, (Stankov, 2012).
Health remains significant for mankind as seen throughout history. Past centuries have observed innovations and discoveries regarding wounds, injury, and health. As early as 2150 BC, rituals for healing were documented for future generations. Samaria tablets noted that wounds should be cleaned with beer and lizard dung applied before bandaging, (Hall, 2007). Centuries later, Greeks and Romans gave great detail regarding the principals of healing. First century AD Roman Celus defined inflammation as a occurrence symptoms. During the 1600’s, Galen designed a model defining its healing power. In the 1800’s further advances in medicine ensued including infection control and cell biology that helped researchers better understand inflammation. In 1863 Germany, pathologist Rudolf Virchow was the first to determine a link between inflammation and cancer. In the 1940’s Menkin, a pathologist, made additional discovers including the biochemical use of proteolysis. However, it wasn’t until the 1950s that significant findings were made regarding the healing process. These include growth factors and cytokines. In the 1990’s researchers found that “heart disease, specifically atherosclerosis (hardening of the arteries)… actually stems from chronic inflammation”, (Guthrie, 2004).
Inflammation is often misunderstood by researchers. It is associated with negative consequences of tissue damage. This is how the body reacts to damage that occurs from irritation, burns, or even infection. Some describe this as a “nonspecific immune response”, (Stankov, 2012). It is most recognized by its symptoms of including redness, heat, swelling, pain, and impairment of function, (Wassung, 2012). Additional symptoms include tenderness and discomfort. All of these are the result of wound repair. It is an important function for defense against injury and a natural response to trauma. The purpose of inflammation is to heal wounds, reduce spreading, clean damaged cells and pathogens, and assist in repair. It is also the first defensive response.
The injured tissue such as proteins and mast cells signal for inflammation chemicals to be delivered to the area through extra cellular fluid. Proteins help to clean out harmful agents and transport nutrients for clotting. The extravasated blood secures the area of injury. Platelets and polymorphonuclear leukocytes initiate the response for inflammation, (Vodovtz, 2010). Leukocytes are significant to this process. They have multiple functions including fighting pathogens and tissue repair. Pro-inflammatory cytokines activate adhesion molecules. Responses also include proteins for clotting and antibodies. These molecules function to assist leukocytes through broken and unbroken walls of blood capillaries. Additional functions of inflammation include sending signals to cytokine network to organize repair and delivering growth. As the inflammation stimulations expanding blood vessels, the area becomes red and hot from restricting blood flow to the area. Pain occurs from the nerve endings as it endures the compression from swelling, nutrients, and discharge of toxins, prostaglandis and kinins, (Wassung, 2012).
The healing response to inflammation includes “over lapping phases of degeneration, inflammation, and regeneration”, (Chen, 2006). Specifically degeneration and inflammation occur first and regeneration occurs last. The length of time varies depends on the scale of injury. However, most wounds begin to reduce swelling within 2 to 3 weeks after tissue damage. T cells and B cells are part of the healing process. They expel biochemical signals for antibodies and immunity. Leukcytes activate cellular programing for the fate and functioning of damaged cells to induce healing. Neutrophils has the ability to organize the phenotype and cytokine of macrophages which promote the growth factor, (Vodovtz, 2010). Macrophages are white blood cells that mobilized and act as a healing agent. Macrophages are controlled by growth factors and pro-inflammatory cytokines. The type of protein used for this healing agent is chemokines macrophage inflammatory protein. It is known to attract platelets, keratin producing cells (keratinocyte), fibroblasts and of course leukocytes. As it excretes from the blood vessels, these cells develop skin or muscle tissue. The macrophages change during this time to offer repair. However repair can only occur under the right conditions. Fibrosis represents the final stages where scaring begins and the wound is nearly repaired. Inflammation is the prerequisite for scarring, (Vodovtz, 2010). With the help of inflammation wounds are able to heal quickly.
Review of Literature
Repair is significant to inflammation. Although inflammation is the initial reaction to injury, regeneration, repair, and remodeling of tissue allow healing to occur. Repair can begin as early as 2 days after injury and can last as long as one year in the remodeling phase. However, fibroblast is required to help rebuild damaged tissue. It helps to produce scar tissue with the use of collagen. The more collagen builds up, the less fibroblast is needed for healing as they begin to create a scar. “It is characterized by remodeling of collagen so as to increase the functional capabilities of the muscle, tendon, or other tissues”, (Ransone, Geissler, Willson, & Adams, 2012). If inflammation persists this is a significant indicator that healing is postponed. This not only increases the potential of scaring but is also characteristic of chronic inflammation. Chronic inflammation has the ability to create an additional list of conditions and problems. It increases the odds of infection and “diseases associated with aging and disability, including heart disease, diabetes, stroke, cancer and Alzheimer’s” (Guthrie, 2004). All of these are conditions associated with chronic inflammation that persists over months and years.
Chronic inflammation is a condition that affects many people especially those with poor immunity. Chronic inflammation is significant to heart disease including strokes. When LDL or harmful cholesterol is built up in the bloodstream, it becomes absorbed by the surrounding tissue. This causes inflammation of the arteries. The swelling associated with inflammation causes blood vessels to enlarge and reduce blood flow creating the right ingredients for a heart attack. “It also plays a significant role in jump-starting other diseases as well, particularly Alzheimer’s disease, diabetes and certain cancers”, (Guthrie, 2004). Additional conditions of chronic inflammation include pancreatitis and Crohn’s disease, (Danovi, 2013). Although there are significant studies relating to this, there is limited evidence that indicate the reasoning for these findings. Researchers suggest that inflammation causing diseases is associated with a dysfunction. This is because of the unique quality of inflammation and the balance between damage and repair.
Many inflammatory cells are known to cause damage to the body. Researchers indicate that neutrophils, white blood cells, cause damage during inflammation before repair occurs to an injury. “Macrophages have also been shown to be capable of promoting muscle damage in vivo and in vitro through the release of free radicals”, (Shen, 2006). The damage these cells cause to unhealed wounds may be associated with their function. For instance, macrophages are also associated with repair and remodeling. Due to this, when macrophages are observed before the repair phase it is likely that these cells are causing damage to the body instead of helping it. When these cells are sent to the area to prepare for healing, they clean the wound from bacteria and other pathogens. However during the process macrophages may unintentionally get rid of debris that is needed for repair, thus slowing the healing process.
Most significant are the findings which indicate “the link between inflammation and cancer”, (Danovi, 2013). When tumors begin to grow and run out of much needed nutrients for growth, macrophages enter the tumor to release cytokines. The cytokines create a cushion for the tumor providing it with molecules and free radicals that encourage tumor growth and cancer cells. In this way, inflammation supports and encourages cancer within the body. Inflammation encourages “most common types of cancer- colon, stomach, lung and breast”, (Guthrie, 2004). Although inflammation is not the direct cause of cancer it has the potential to exacerbate risks. This is because inflammation cells provide tumors the right environment for growth. The majority stems from DNA. Inflammation damages the DNA of tumors that causes tumors to mutate into full blown cancer from free radicals and molecules released inside the tumor. As such colon cancer is said to be “the most common cancer that feeds on inflammation”, (Guthrie, 2004).
Many studies demonstrate the relationship between cancer and inflammation. This is closely related to tumors that develop in the body that encourage cancer. It is important to understand that chronic and acute inflammation does not determine the onset of cancer. Many professionals use drugs and other strategies related to inflammation. Studies show that, “drugs inhibit the production of prostaglandins during inflammation reduce the risk of various cancers, such as colorectal, esophageal, gastric, lung, breast, and ovarian cancer”, (Kamp, Shacter, & Weitzman, 2011). These include aspirin and ibuprofen. Despite this, inflammation is observed in and around any tumor present in the body. Immune cells are found in these areas. They include cytokines and chemokines that can be both helpful and harmful. Macrophages also play an important role in this phase. The use of proteins encourages tumor growth however not intentionally. Many studies show that high levels of these molecules are found inside tumors indicating it’s harmful effects.
Arguments for Study
Inflammation continues to be explored and examined as researchers attempt to better understand the positive and the negative qualities of the immune response. As such, inflammation continues to be a balance that is very complex. Those interested in the process often seek to limit the symptoms and deter inflammation. Yet some argue this may affect how the body reacts to the healing process. Limiting inflammation may cause healing to occur at a slower pace. This can be either beneficial or harmful. For instance researchers have discovered a link between inflammation and Alzheimer’s disease. Some studies suggest that the use of ibuprofen over an extended period of time reduces the risks of Alzheimer’s disease, (Guthrie, 2004). This is because ibuprofen decreases swelling of the brain. However, this is just speculation.
The role that cytokine play in the process of inflammation remains in question. Researchers found that agents produce a response that stimulates cytokine engagement. This stimulates inflammation. Other studies found that cytokine also has a major part in anti-inflammation. When studying these cells in mice with colon adenomas, it illustrates “the preventive and therapeutic potential of anti-inflammatory cytokine”, (Karin, Lawrence, & Nizets, 2006). The finding argues against previous research suggesting that inflammation can encourage cancerous growth. Yet, when cytokine T-cells were injected into the subjects, it created a counter reaction. This was only observed in early stages of cancer and with malignant and negatively regulated T-cells.
When tumors are present in the body, the body attempts to fight against the harmful agent. It attempts to use various proteins to weaken the tumor but instead it is a catalyst for growth. The DNA observed within these cells change when entering the tumor to fight it. The damage which occurs to the DNA is large and significant. Many argue that genes and stress relate to how much damage happens within these structures. These damages cause mitochondrial dysfunction along with other problems including redirecting cellular structures and also death of additional cells. As a result, “mutations from some inflammation-associated stress are evident in the epithelium of cancer cells and in inflamed epithelial cells”, (Kamp, Shacter, & Weitzman, 2011). Due to the effects this has on the body, researchers are surprised to find that changes in DNA are the result of chronic inflammation that can increase the risks of cancer.
Additional arguments relating to chronic inflammation include strategies for prevention. There are various options that professionals use. One method to combat inflammation is thermo therapy. Research found that adding additional heat to a wound or injury will improve inflammation and healing. However, “for unknown reasons therapist have been reluctant to use this technique for treatment of acute inflammatory conditions”, (Stankov, 2012). Heat can be applied physically or with the use of pharmaceutical chemicals. Another method of anti-inflammatory is diet. Research found that fats such as omega 3’s act as anti-inflammatory agents. Other foods such as herbs also help to combat the problem. An anti-inflammatory diet consists of “cutting back on meat and high-fat dairy foods” as well as fish oil, (Guthrie, 2004). The study suggests that when the diet is changed, it has the potential to decrease inflammation by as much as 30%, (Guthrie, 2004).
For future research, professionals must understand the complex dynamics of inflammation. This should start with the definition and understanding of the phenomenon. “Inflammation embraces a great variety of biological processes”, (Scott, Khan, Cook, & Duronio, 2004). This is because it cleans wounds, repairs, injuries, and begins the scaring process. For this reason, researchers need to better understand the process of inflammation to better determine the need to reduce inflammation or encourage inflammation in the body. It occurs in a number of stages and does not completely retreat until the wound has recovered from injury. Once the phenomenon is better understood, scientist can better control and regulate the process by modulating the factors for healing.
Trends for further study have the potential to improve therapeutic treatment of inflammation. This can be done by “targeting the stomal macroenvironment in general, and tissue fibroblasts in particular, is likely to be an important target… for therapy”, (Buckley, Lord, Akbar, Scheel-Toellner, & Salman, 2001). Examining the environment that stimulates inflammation and the use of fibroblasts for healing can help to reduce the onset of cancer. This is because of the cushion that inflammation has and its ability to feed cancer cells. With additional information about the relationship between fibroblasts, macrophages, and other inflammatory cells, professionals can better control the immunity that the body produces when cancer occurs. Understanding how the body response to damage control, researchers can limit the inappropriate production of inflammatory responses to allow for a transition from a helpful agent into a harmful one.
Fibroblasts continue to be an interest for researchers due to its relationship to the immune system, inflammation, and cancer. It regulates cells around damaged tissue including cytokines and chemokines. Fibroblasts act as white blood cells and are supposed to be beneficial to the body however instead it can be harmful. It has the ability to over excite the immune system. This over excitement may be significant to tumors and cancerous cells. Instead of fighting these cells, fibroblasts help to feed the process. It causes further damage to tumors such as mutation of cells and the killing of immunity cells. Studies found that fibroblasts mutate once encountering the damaging agents. The fibroblasts alter in phenotype once entering damaged tissue. These mutations include DNA and gene mutations that are reborn in cells thus causing harm. Finding the cause of this mutation, researchers have the potential to reduce cancer and allow inflammation cells to fight against disease. In this way, “the molecular basis for the persistent, activated phenotype of fibroblasts at sites of chronic inflammation remains unclear”, (Buckley, et al., 2001). It stresses the importance for researchers to address these issues to resolve the issue of cancer and tumors.
Researchers define the phenomenon of inflammation bests, “inflammatory cells promote both injury and repair through continued actions of free radicals, growth factors, and chemokines”, (Sheen, 2006). It is a defensive shield and part of human immunity. The phenomenon is required for human survival and guides recovery from internal and external injuries. When inflammation is prolonged or becomes chronic, it can be damaging. It has the ability to cause heart disease and encourage cancer development. With additional studies and research, understanding inflammation can reduce various health conditions and save lives. It can reduce Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and atherosclerosis, peptic ulcers, and more, (Karin, Lawrence, & Nizet, 2006). Researchers must better understand the effect of inflammation and the need to reduce this when injuries occur. Some professionals question strategies used to reduce inflammation due to the helpful agents it has during injury. However, this is a delicate measure as prolonged inflammation can have such disastrous effects. With research, modification, and control measures professionals can ensure that inflammation becomes recognized for its healing agents versus its harmful ones.
- Buckley, C., Pilling, D., Lord, J., Akbar, A., Scheel-Toellner, D., & Salmon, M. (2001). Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. TRENDS in Immunology 22(4) p. Retrieved from: http://users.ugent.be/~ddegroot/SBO_STRETCH/27_Lefevre_2009.pdf
- Danovi, S. (2013). Feeling the heat- the link between inflammation and cancer. Cancer Research UK—Science blog. 01, 2013. Retrieved from: http://scienceblog.cancerresearchuk.org/2013/02/01/feeling-the-heat-the-link-between-inflammation-and-cancer/
- Eming, S., Krieg, T., Davidson, J. (2007). Inflammation in wound repair: Molecular and cellular mechanism. Journal of Investigative Dermatology. 127(2) p. 514-25. Retrieved from: http://www.nature.com/jid/journal/v127/n3/full/5700701a.html
- Guthrie, C. (2004). Fighting Inflammation. Experience Life Magazine. July/August 2004 edition. Retrieved from: https://experiencelife.com/article/fighting-inflammation/
- Karin, M., Lawrence, T., Nizet., V. (2006). Innate immunity gone awry: Inking microbial infections to chronic inflammation and cancer. Cell 124(4) p. 823-35. Retrieved from: http://www.sciencedirect.com/science/article/pii/S0092867406001917
- Kamp, D., Sacter, E., & Weitzman, S. (2011). Chronic inflammation and cancer: The role of the mitochondria. Oncology Journal. Review April 30, 2011. Retrieved from: http://www.cancernetwork.com/articles/chronic-inflammation-and-cancer-role-mitochondria/page/0/2
- Ransone, J., Geissler, G., Wilson, P., Adams, B. (2012). Soft Tissue Damage and Healing. IAAF Medical and Anti Doping Commision.
- Scott, A., Khan, K., Cook, J., Duronio V. (2004). What is “inflammation”? Are we ready to move beyond celsus. Behavior Journal of Sports Medicine. 38(4) p. 248-249. Retrieved from: http://bjsm.bmj.com/content/38/3/248.full.pdf+html
- Shen, W. (2006). The role of inflammation in skeletal muscle healing. Shanghi Second Medical University. University of Pittsburg. School of Enginnering and Doctor of Phiosophy. Retrieved from: http://d-scholarship.pitt.edu/6559/1/WeiShen_2006.pdf
- Stankov, S. (2012). Definition of inflammation, causes of inflammation and possible anti-inflammatory strategies. The Open Inflammation Journal. 5(2) p. 1-9. Retrieved from: http://benthamopen.com/toinfj/articles/V005/1TOINFJ.pdf
- Wassung, K. (2010). The role of inflammation in the healing process. Retrieved from: http://www.nature.com/jid/journal/v127/n3/full/5700701a.html
- , J. (2002). Inflammatory Mediators and Cell adhesion molecules as indicators of Severity of Atherosclerosis: The Rotterdam Study. Arterioscler Thromb Vascular Biology. 22(3). 838-842. Retrieved from: http://atvb.ahajournals.org/content/22/5/838.full.pdf