Lymphedema at the Molecular Level
What is Inflammation?
Lymphedema affects the immune system and leads to a common reaction amongst people which is known as inflammation. Generally, inflammation is triggered by the immune system to remove harmful or irritating stimuli from within the body. There are four main symptoms that indicate inflammation including heat, redness, pain, and swelling. Inflammation involves a series of changes that release various substances or molecules into the circulatory system. These changes can increase blood flow, pain signals, and fluid into the affected tissue (1). Specifically, the main molecular pathway that is involved with inflammation is the expression of pro-inflammatory molecules called cytokines (2).
Lymphedema and Cytokine Expression
Cytokines are small protein molecules that are released by the immune system when encountering stress (2). These cytokines play an important role in communicating between your immune system and the rest of the body. They initiate responses in your body to protect against harmful substances in certain body parts by promoting inflammation, which is a key feature of lymphedema. In individuals with lymphedema, the number of cytokines that are made by the immune system increases. This causes inflammation to be activated more quickly and for a longer period of time in certain tissues. This can lead to painful and uncomfortable symptoms such as swelling, aching and skin changes in the affected areas.
Lymphedema and Antigen Processing
Additionally, antigen processing is an important molecular pathway that helps to fight off harmful substances and infections (2). Antigens are proteins that are commonly recognized by the white blood cells in the body as harmful substances from a bacterial, viral or other type of infection or disease. Once the white blood cells recognize the antigens, they process these antigens to create antibodies and trigger other immune responses to combat any harmful substances in the affected areas. With lymphedema, the accumulation of fluid causes the immune system to get disrupted, also known as immunosuppression. This immunosuppression is caused by the lack of antigen transport to areas which are populated with white blood cells that can recognize them and get rid of the harmful substances. Immunosuppression causes individuals with lymphedema to be highly susceptible to recurrent infections.
References
(1) Institute for Quality and Efficiency in Health Care (IQWiG). (2018). What is an inflammation? In NCBI. IQWiG. https://www.ncbi.nlm.nih.gov/books/NBK279298/
This article examines inflammation in lymphedema patients. More specifically it discusses the causes, such as pathogens and external injuries, along with some signs that inflammation is occurring, such as redness, heat, and pain. The article continues to further discuss what happens in the body and body responses when inflammation is occurring.
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(2) Ly, C., Kataru, R., & Mehrara, B. (2017). Inflammatory Manifestations of Lymphedema. International Journal of Molecular Sciences, 18(1), 171. https://doi.org/10.3390/ijms18010171
This resource investigates and focuses on the current research behind the pathophysiological changes in lymphedema and how a lack of understanding in this area could be a reason there is no cure for lymphedema. Recent finding outline that the inflammatory response and process may play a key part in further determining the pathology of the disease.
Media References
(1) Burgard, C., Baumeister, R., Strobl, F., Rominger, A., Bartenstein, P., Wallmichrath, J., Frick, A., Notohamiprodjo, M., & Weiss, M. (2014). Magnetic resonance imaging versus lymphoscintigraphy for the assessment of focal lymphatic transport disorders of the lower limb. Nuklearmedizin, 53(05), 190–196. https://doi.org/10.3413/nukmed-0649-14-03
This resource outlines the comparison made between the diagnostic accuracy of magnetic resonance imaging and lymphoscintigraphy for the purpose of assessment of focal lesions of the peripheral nervous system.
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(2) Li, C. Y., Kataru, R. P., & Mehrara, B. J. (2020). Histopathologic Features of Lymphedema: A Molecular Review. International Journal of Molecular Sciences, 21(7), 2546. https://doi.org/10.3390/ijms21072546
This article focuses on secondary lymphedema more specifically the pathogenesis of secondary lymphedema. Recent studies have outlined that secondary lymphedema is more complex than previously thought, as inflammation, infections, and adipogenesis contribute to lymphedema. Studies focused on this research could potentially discover a therapy for lymphedema.
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