Introduction
Inflammation is a dynamic process with cardinal signs of redness, swelling, heat, and pain. Scientific investigations have revealed that cells, chemical components, and pathways are involved in inflammation. The body’s initial defense in response to inflammation is through an acute phase (short-term response). The acute response sets through systemic reactions seen shortly after a triggering event. One of the primary aspects is the increased liver synthesis of positive acute-phase proteins (APPs), also called inflammatory markers (or biomarkers). As a result, it leads to an increased concentration of the markers in the blood. Further, the serum level of these markers returns to base concentration when the trigger is absent. These markers of inflammation are crucial, as an inflammatory response is impossible without them. Also, they are used as diagnostic and therapeutic targets for various inflammatory diseases.
What Is the Importance of Inflammatory Markers?
Inflammation is initiated by infection, trauma, or injury through a cascade of various leukocytes (white blood cells) and cytokines inflammatory mediators). Even the injured or dead tissues release inflammatory mediators. To mediate inflammation, cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and interleukin-6 (IL-6) play vital roles in activating neutrophils, macrophages, and monocytes (inflammatory cells). Activated leukocytes trigger an acute-phase response through the manifestation of fever, leukocytosis, and the production of various inflammatory markers.
These inflammatory markers are secreted by the liver under the influence of cytokines. Then, they flow through the bloodstream, reach the inflammation site, and remove the pathogens.
The changes in serum concentrations of the inflammatory markers are due to the altered synthesis from the liver. Animal models for inflammatory diseases are being developed to understand inflammation, identify inflammatory markers, and their role in treatment.
A biomarker is a criterion (chemical, physical, or biological) that can be applied to diagnose or detect the disease’s progress. Biomarkers also represent alterations in the body constituents. Further, scientists can compute the results of treatment in research. These markers provide a medium for disease classification and understanding the disease mechanism. Biomarkers provide a dynamic tool to grasp the spectrum of inflammatory diseases, clinical trials in populations, and screening with diagnosis and prognosis. Biomarkers can also reflect the earliest symptoms of the terminal stages. An assessment of the validity of biomarkers is required to correlate with the disease stage. However, variability in the measurement of biomarkers ranges from laboratory errors to machine dysfunction, improper storage of body fluid, and other issues.
What Are the Various Important Inflammatory Markers?
Inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma viscosity (PV), are used in primary care for the diagnosis and monitoring of inflammatory conditions.
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ESR is defined as the distance in millimeters that erythrocytes (red blood cells) settle in whole blood in an hour.
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Plasma viscosity is another test that measures blood thickness (viscosity). It is done by calculating the force required for plasma (liquid portion of the blood) to settle down in a test tube in a given time. During inflammation, blood thickness (or viscosity) increases due to raised blood protein levels. Plasma viscosity is considered to be superior to ESR. It is because it is unaffected by the factors that affect ESR (age, gender, low hemoglobin).
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CRP has a primary role in tissue alteration and inflammation. It is considered superior for infections as it rises more rapidly than ESR and plasma viscosity in response to inflammation. Further, it is not affected by external factors.
The inflammatory biomarkers responsible for the pathology of inflammatory disease are diverse. Hence, various other inflammatory markers that increase in inflammatory conditions are serum amyloid A (raised in joint diseases), haptoglobin (produced by the liver), and fibrinogen (a clotting factor raised in heart diseases).
All the inflammatory markers help restore balance and reduce microbial growth during trauma, stress, or infection. Antioxidant defense systems (antioxidant enzymes) influence oxidative stress. Increased oxidative stress levels can induce the production of reactive oxygen species (ROS). Thus, this cascade can increase gene expression encoding growth factors, inflammatory cytokines, and chemokines. Oxidative stress is implicated in multiple disease mechanisms, such as heart disease, cancer, diabetes mellitus, hypertension, aging, and atherosclerosis. Therefore, oxidative stress products can also be used as inflammatory markers.
Can Inflammatory Markers Diagnose a Disease?
Medical decisions cannot be made entirely on the results of an inflammatory marker test. Abnormal inflammatory marker test results suggest inflammation. However, they do not identify the cause. It is because the inflammatory markers are non-specific, and the diagnosis may be a viral infection or cancer. Also, raised inflammatory markers do not always indicate a disease, as they can also increase in obese individuals (as inflammation plays a role in obesity).
Clinicians may take note of the symptoms and suggest a relative test. If a patient has symptoms of a specific condition, a raised inflammatory marker may diagnose that condition. It is true in diseases such as polymyalgia rheumatica (PMR; an inflammatory disorder causing muscle pain and stiffness) and temporal arteritis (inflammation of the arteries around the scalp). In these diseases, a raised inflammatory marker blood test and typical symptoms can lead to a diagnosis.
During inflammation, rising inflammatory markers may suggest a poor response to treatment. On the contrary, decreasing inflammatory markers can indicate a good treatment response. Inflammatory markers can diagnose or monitor inflammatory conditions such as inflammatory bowel disease (IBD; a long-standing inflammation of the digestive tract), rheumatoid arthritis (RA; an inflammatory joint disease that affects young individuals), systemic lupus erythematosus (SLE; an autoimmune disorder), PMR, temporal arteritis, infections, and cancers. Sometimes, doctors use inflammatory markers as a non-specific test to rule out serious diseases.
Inflammatory markers are used in clinical applications to differentiate normal from pathogenic processes. Inflammatory markers may be predictive of inflammatory diseases and also correlate with the consequences of various inflammatory diseases. Pathogenic stimuli activate inflammatory cells and induce the production of inflammatory proteins and enzymes. These molecules can potentially serve as biomarkers for disease diagnosis, prognosis, and decision-making regarding treatment.
Conclusion
Recently, a plethora of inflammatory diseases have increased concerns regarding global health. Hence, continued clinical research is taking place to understand different inflammatory disease mechanisms for efficient and safe pharmacological treatment modalities. These diseases pose a nuisance to global health and also obstruct socioeconomic development. Therefore, research should be done in genetic and molecular areas to improve the diagnosis and treatment of such diseases.
