Acute phase protein

Acute phase proteins (APPs), also called acute phase reactants, are proteins whose synthesis is up- or downregulated in case of inflammation, both acute and chronic (despite the name). This is called the acute phase reaction or acute phase response, which is part of the body's defence against microbes. Acute phase proteins are produced in the liver.

Triggers of the acute phase reaction

When certain immune cells, mostly macrophages and monocytes, are stimulated by a microbe or other noxious stimulus, they secrete cytokines. The cytokine interleukin 6 (IL-6), as well as IL-1 beta, tumor necrosis factor alpha, and interferon gamma, are released. These cytokines reach the liver and triggers the liver to regulate the acute phase proteins.

Positive acute phase proteins

Positive acute phase proteins are those proteins whose synthesis is upregulated during inflammation. Following the acute phase reaction the positive acute phase protein concenctration increases up to 1000-fold. The positive acute phase proteins have beneficial effects against microbes. The positive APPs are:

• C-reactive protein (CRP)
• Serum amyloid A (SAA)
• Fibrinogen
• Alpha-1 antitrypsin
• Haptoglobin
• Ferritin
• Hepcidin
• Procalcitonin

The increase in positive APPs, especially fibrinogen, causes the erythrocyte sedimentation rate to increase in case of inflammation.

Negative acute phase proteins

Negative acute phase proteins are those proteins whose synthesis is downregulated during inflammation. This is mostly so that the liver can redirect available amino acid to synthesis of positive acute phase proteins. The negative APPs are:

• Albumin
• Transferrin
• Transthyretin
• Antithrombin

The levels of some non-protein compounds in the body also decreases in response to inflammation. This is true for iron, vitamin D, and zinc.

Other effects of the acute phase reaction

The aformentioned cytokines also stimulate other responses in the body, including fever, sickness behaviour, and leukocyte production in the bone marrow. In cases of chronic inflammation, the cytokines also have unwanted effects, like cachexia, muscle wasting, anaemia of chronic disease, and impaired growth in children.