The primary reaction of the body to immunological stress is the innate, non-specific response that will precede specific immune reactions. The acute phase response (APR) is a prominent systemic reaction of the organism to local or systemic disturbances in its homeostasis caused by infection, tissue injury, trauma or surgery, neoplastic growth or immunological disorders.
At the site of invasion by a micro-organism and the place of tissue injury, a number of responses of the tissue itself are initiated. Pro-inflammatory cytokines are released, and the vascular system and inflammatory cells are activated. These responses in turn are associated with production of more cytokines and other inflammatory mediators which diffuse to the extracellular fluid compartment and circulate in the blood.
Early phase response factors
Different low molecular weight peptide mediators are known to be secreted by activated leukocytes (interleukins) and other cells. They are collectively termed cytokines and are involved in triggering the APR.
Three main groups of cytokines can be distinguished:
– Cytokines that primarily act as positive or negative growth factors for a variety of cells (IL-2, IL-3, IL-4, IL-7, IL-10, IL-11, IL-12 and CSF2),
– Cytokines with pro-inflammatory properties (TNF-α/β, IL-1α/β, IL-6, IFN-α/γ, IL-8, and macrophage inhibitory protein-1/CCL3),
– Factors with anti-inflammatory activity (IL-1 receptor antagonists, soluble IL-1 receptor, TNF-α binding proteins and IL-1 binding proteins).
The second group of cytokines is likely to be the most important in the induction of APR. Pro-inflammatory cytokines are responsible for induction of fever and muscle catabolism, but they also activate white bone marrow blood cell precursors, growth of inflammatory tissue fibroblasts and macrophages to amplify the response.
Acute phase response factors
During the APR, plasma viscosity largely increases as a result of the total changes in total blood protein concentration.
These acute phase proteins (APP) can be separated in several groups:
– Proteins whose concentrations increase by about 50%: ceruleoplasmin, C3 complement protein,…
– Proteins that will increase 2 or 3 fold: fibrinogen, haptoglobin, AAG, AHSG,…
– Proteins whose production is increased 50 to 1000 times: CRP, SAA, PCT…
APPs can be generated either during acute inflammation process or also during permanent stimulations (such as chronic infections). During the latter, APPs levels remain elevated in comparison to normal values and can often be used for diagnosis purposes.