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Acute phase reactants

Author
Irving Kushner, MD
Section Editor
Daniel E Furst, MD
Deputy Editor
Paul L Romain, MD

INTRODUCTION

An increase in the concentration of serum proteins that are referred to as acute phase reactants (APR) accompanies inflammation and tissue injury [1,2]. Focus on the acute phase phenomenon, termed the acute phase response, first occurred with the discovery of C-reactive protein (CRP) in the serum of patients during the acute phase of pneumococcal pneumonia [3,4]. During the acute phase response, usual levels of various proteins maintained by homeostatic mechanisms can change substantially. These changes are thought to contribute to host defense and other adaptive capabilities.

A discussion of the biology of the acute phase response; the general clinical utility and interpretation of measurement of APR, such as CRP; and the clinical utility of indirect measures of the acute phase response, such as the erythrocyte sedimentation rate (ESR), are presented here. Detailed reviews of disorders associated with variations in APR and the utility of APR measurements in specific conditions, the innate immune response, and the role of cytokines in immunity and inflammation are described separately (see appropriate topic reviews of individual clinical disorders). (See "An overview of the innate immune system" and "Role of cytokines in the immune system".)

THE ACUTE PHASE RESPONSE

Definition and regulation — Despite its name, the acute phase response accompanies both acute and chronic inflammatory states associated with a wide variety of disorders, including infection, trauma, infarction, inflammatory arthritides and other systemic autoimmune and inflammatory diseases, and various neoplasms. Acute phase proteins are defined as those proteins whose serum concentrations increase or decrease by at least 25 percent during inflammatory states [1]. Such proteins are termed either positive or negative acute phase reactants (APR), respectively. The erythrocyte sedimentation rate (ESR), a nonprotein or indirect APR, reflects plasma viscosity and the presence of acute phase proteins, especially fibrinogen, as well as other influences, some of which are as yet unidentified [5]. (See 'Erythrocyte sedimentation rate' below.)

Changes in the levels of APR largely reflect altered production by hepatocytes, resulting primarily from the effects of cytokines produced during the inflammatory process by macrophages, monocytes, and a variety of other cells. Interleukin (IL)-6 is the major inducer of most APR [6]. Some of the other major cytokines relevant to the acute phase response are IL-1 beta, tumor necrosis factor (TNF)-alpha, and interferon gamma. These cytokines also suppress the synthesis of albumin, which is termed a “negative APR” because its levels decrease with inflammation [7]. Combinations of cytokines can have additive, inhibitory, or synergistic effects, and patterns of cytokine production differ under various inflammatory conditions [8-10]. (See "Role of cytokines in rheumatic diseases".)

Increases in APR can vary from approximately 50 percent for ceruloplasmin and several components of the complement cascade to 1000-fold or more for C-reactive protein (CRP) and serum amyloid A (SAA). Additional positive APR include fibrinogen, levels of which have substantial effects on the ESR; alpha-1 antitrypsin; haptoglobin; IL-1 receptor antagonist; hepcidin; ferritin; procalcitonin; and others [8,11,12]. Negative APR include albumin, transferrin, and transthyretin.

               

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Literature review current through: Jun 2015. | This topic last updated: Apr 14, 2015.
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