Acute Phase Response Signaling

The acute phase response is a rapid inflammatory response that provides protection against microorganisms using non-specific defense mechanisms. In addition to infection it can also be triggered by tissue injury, trauma or surgery, neoplastic growth or immunological disorders. Typically it consists of fever, an increase in inflammatory factors (such as pro-inflammatory cytokines) and a change in concentration of several plasma proteins (the acute phase proteins) due largely to an altered hepatic metabolism. This response is mediated by endogenous pyrogens, the hypothalamus, adrenal hormones and other factors. Pro-inflammatory cytokines have other effects as well, such as suppression of cytochrome P450 enzymes, which has a large impact on the metabolism and toxicity of various chemical compounds and drugs. As part of the response the negative acute phase response proteins are downregulated. Many of the negative acute phase response proteins bind hormones such as cortisol and retinol, theirdownregulation results in an effective increase in hormone availability.

Positive acute phase response proteins are upregulated during the response and increased levels in the plasma become measurable as early as 4-5 hours after a single inflammatory stimulus. After a single stimulus the levels of these proteins remain elevated for at least 24 hours and decrease after about 48 hours. Positive acute phase response proteins have general functions in opsonization and trapping of micro-organisms, complement activation, neutralizing enzymes and modulating the immune response.