The acute phase response (APR) is the body’s immediate, widespread reaction to harms like infection or injury. This rapid, non-specific defense mechanism responds generally to different threats rather than targeting a specific pathogen. It involves a cascade of systemic physiological changes to address the initial insult and restore balance.
How the Body Initiates the Response
The acute phase response is activated by common triggers including infections caused by bacteria, viruses, fungi, or parasites, as well as tissue injuries from trauma, surgery, or burns. Conditions like myocardial infarction (heart attack) or certain autoimmune diseases can also initiate this systemic reaction. At the site of injury or infection, immune cells such as macrophages and other leukocytes detect molecular patterns associated with pathogens or damaged cells.
Upon detection, these immune cells release signaling molecules called cytokines into the bloodstream. The primary cytokines involved in initiating the acute phase response are interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1). These cytokines then travel through the blood to various organs, particularly the liver, to coordinate the widespread systemic response.
Changes Within the Body During Acute Phase Response
The acute phase response causes various physiological changes and common symptoms. These include fever, which helps defend against microbial invasion and inhibit pathogen growth. Individuals may also experience fatigue, loss of appetite, and altered sleep patterns.
A central aspect of the APR is the liver’s role in producing acute phase proteins (APPs). These proteins, whose concentrations can increase dramatically or decrease, are synthesized primarily by hepatocytes in response to inflammatory cytokines. Examples of positive APPs, which increase, include C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen. CRP, for instance, binds to microbial cell walls and damaged human cells, aiding in their removal and activating the complement system.
Serum amyloid A (SAA) proteins also increase significantly and are involved in transporting cholesterol and recruiting immune cells to inflammatory sites. Fibrinogen, a coagulation factor, increases to promote endothelial repair and can lead to a faster erythrocyte sedimentation rate (ESR), a common marker for inflammation. Conversely, some proteins, known as “negative” acute phase proteins, decrease in concentration, such as albumin and transferrin, to conserve amino acids for the production of positive APPs. Metabolic shifts also occur, including changes in iron and zinc levels, as the body redirects resources for defense and repair.
The Purpose of the Acute Phase Response
The acute phase response serves as an early, rapid defense mechanism against various threats. It helps contain infections by trapping microbes in blood clots through coagulation factors like fibrinogen. The response also neutralizes toxins and clears cellular debris from damaged tissues.
The APR promotes tissue repair and wound healing, restoring the body’s internal balance. Acute phase proteins, such as C-reactive protein and mannose-binding protein, function as soluble pattern-recognition receptors, enabling the body to identify foreign substances early in the infection process. This coordinated systemic reaction provides immediate protection before specific immune responses are fully activated.
When the Response Persists
When the acute phase response becomes prolonged or dysregulated, it can lead to chronic inflammation, with significant clinical implications. Persistent activation means the body continues to send inflammatory cells even when the initial danger has passed, which can result in long-term damage. This sustained inflammatory process contributes to the development or progression of various chronic diseases.
Chronic inflammation is linked to autoimmune conditions like lupus and rheumatoid arthritis, where the immune system mistakenly attacks healthy tissues. It also plays a role in cardiovascular diseases, including heart disease and high blood pressure, and metabolic syndrome, with associations to Type 2 diabetes. Certain neurological disorders and some cancers are also connected to persistent inflammatory states. For example, prolonged elevation of serum amyloid A proteins can lead to secondary amyloidosis, a condition where abnormal protein deposits accumulate in organs.