Mon Jul 05 2021
What are Inflammatory Biomarkers?
Inflammation is not a disease or a disorder. On the contrary, inflammation is the response of the body’s immune system to a disease or a disorder, or an injury. The inflammatory response of the body can occur in a number of scenarios. For instance, the body has an inflammatory response in cancerous conditions, when invaded by an infectious agent, or when exposed to any physical trauma, etc1.
During an inflammatory response, certain biological molecules are released into the bloodstream. Alterations in the concentrations of these molecules can serve as biomarkers for inflammation. Inflammatory biomarkers are highly beneficial in clinical practice, as the presence or absence of inflammation can help diagnose diseases and also rule out various conditions1. Inflammatory biomarkers can also be used to monitor the treatment progression of certain diseases. This article will discuss the main types of inflammation, the important inflammatory biomarkers measured in clinical practice, and the effectiveness of suPAR as an inflammatory biomarker1.
Types of Inflammation: Acute and Chronic
Inflammation can be divided into two main types: acute and chronic. Acute inflammation generally occurs in response to an external injury or sudden onset of an illness. The inflammatory response observed in acute inflammation is of short duration and can last from several minutes to days depending on the severity of the injury or illness. A person can develop varying symptoms during an acute inflammatory response2 . For example, in infection diseases, a person can develop fever or in case of an injury, a person can have redness, pain, and restricted mobility in the affected area of the body. Acute inflammation is reversible and with proper care and treatment of the underlying disease or injury, the inflammatory changes can be treated2.
On the other hand, chronic inflammation can develop over months or years. It is usually seen in long-standing conditions such as rheumatoid arthritis, vasculitis, pulmonary fibrosis, etc. Chronic inflammation can cause irreversible damage to the affected tissue due to formation of scar tissue in the affected organs. This can severely compromise tissue function over time. For example, chronic inflammation in rheumatoid arthritis can cause joint immobility3 .
Which Biomarkers are Measured to Detect Inflammation?
The important and commonly measured inflammatory biomarkers in clinical practice are as follows4 :
- Cytokines (chemokines): These are small soluble proteins that mediate and regulate the process of inflammation. Usually, cytokines act at very low concentrations in a short time span. In cancerous diseases, the malignant tumors can cause cytokine production. Currently, cytokines are vital inflammatory biomarkers that can be directly measured via serum or plasms samples in several types of cancers. The level of cytokines in the bloodstream can also help determine the stage of the tumor and the extent of the disease.
- C-reactive Protein: This is a protein produced by the liver cells during inflammation. It is a non-specific marker of inflammation that could be useful in determining inflammatory response in colorectal and lung cancers.
- Serum Amyloid A (SAA): SAA is more responsive to inflammation than CRP. It is strongly associated with worse long-term survival in breast cancer patients.
- 8-hydroxy-2’-deoxyguanosine: This is a sensitive surrogate biomarker which indicates in vivo oxidative stress. Elevated levels can be observed in different types of cancer including esophageal, colon and breast cancer.
- COX-2 Expression: This enzyme is expressed in almost every type of tumor.
suPAR as an Inflammatory Biomarker
suPAR is a strong non-specific biomarker of inflammation. In chronic inflammation or during immune activation, uPAR is released from the cell membrane and becomes soluble (suPAR). Hence, the suPAR level in the bloodstream reflects the extent of immune activation in the individual. When attached to the cell membrane, uPAR is involved in several functions of the inflammatory response5,6 . The following research studies support the use of suPAR as an inflammatory biomarker:
- A study published in 2014 in the Journal of Clinical Microbiology found that suPAR is the most promising prognostic biomarker in the identification of early systemic inflammatory response syndrome (SIRS). In this study, as a prognostic marker suPAR was reported to be superior to C-reactive Protein and Procalcitonin7 .
- In 2015, a report published in Endocrine Today suggested that suPAR is a reliable and sensitive marker of inflammation. The report was based on a study of urogenital tract inflammation. As per the report, suPAR can be sensitive marker of inflammation that is limited to a localized area8 .
- A study published in 2017 in the International Journal of Cancer reported that as an inflammatory biomarker suPAR is strongly associated with cancerous conditions9 .
1. Chen et.al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018. 9(6).
2. Ross AC. Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis. The American Journal of Clinical Nutrition. 2017. Vol 106: 6.
3. Pahwa R, Singh a, Jialal L. Chronic Inflammation. StatPearls Publishing LLC. 2019.
4. Brenner et.al. A review of the application of inflammatory biomarkers in epidemiologic cancer research. Cancer Epidemiology, Biomarkers & Prevention. 2014. 23(9).
5. Thunø M, Macho B, Eugen-Olsen J. suPAR: The molecular crystal ball. Dis Markers. 2009;27(3):157-72. 2. Eugen-Olsen, J. et al. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J. Intern. Med. 2010;268, 296–308.
6. Smith HW, Marshall CJ. Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol 2010;11(1):23–36.
7. Reichsoellner et.al. Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome. Journal of Clinical Microbiology. 2014.
8. Grande et.al. Poster Board THR- 135. Presented at The Endocrine Society Annual Meeting; March 5-8; 2015. Source: Endocrine Today.
9. Rasmussen et.al. Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer. International Journal of Cancer. 2017. Vol 141: Issue 1.