Role of C-Reactive Protein at Sites of Inflammation and Infection

Abstract

C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation. CRP is produced as a homopentameric protein, termed native CRP (nCRP), which can irreversibly dissociate at sites of inflammation and infection into five separate monomers, termed monomeric CRP (mCRP). CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes. Evidence suggests that estrogen in the form of hormone replacement therapy influences CRP levels in the elderly. Having been traditionally utilized as a marker of infection and cardiovascular events, there is now growing evidence that CRP plays important roles in inflammatory processes and host responses to infection including the complement pathway, apoptosis, phagocytosis, nitric oxide (NO) release, and the production of cytokines, particularly interleukin-6 and tumor necrosis factor-α. Unlike more recent publications, the findings of early work on CRP can seem somewhat unclear and at times conflicting since it was often not specified which particular CRP isoform was measured or utilized in experiments and whether responses attributed to nCRP were in fact possibly due to dissociation into mCRP or lipopolysaccharide contamination. In addition, since antibodies for mCRP are not commercially available, few laboratories are able to conduct studies investigating the mCRP isoform. Despite these issues and the fact that most CRP research to date has focused on vascular disorders, there is mounting evidence that CRP isoforms have distinct biological properties, with nCRP often exhibiting more anti-inflammatory activities compared to mCRP. The nCRP isoform activates the classical complement pathway, induces phagocytosis, and promotes apoptosis. On the other hand, mCRP promotes the chemotaxis and recruitment of circulating leukocytes to areas of inflammation and can delay apoptosis. The nCRP and mCRP isoforms work in opposing directions to inhibit and induce NO production, respectively. In terms of pro-inflammatory cytokine production, mCRP increases interleukin-8 and monocyte chemoattractant protein-1 production, whereas nCRP has no detectable effect on their levels. Further studies are needed to expand on these emerging findings and to fully characterize the differential roles that each CRP isoform plays at sites of local inflammation and infection.

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

“…Several reports also focused on lymphopenia and high levels of C-reactive protein in COVID-19 patients [20,21]. C-reactive protein is a biomarker with highsensitivity for inflammation and host response to the production of cytokines, particularly TNFα, IL-6, MCP1 and IL-8 secreted by T cells [26]. However, most mechanistic studies suggest that C-reactive protein itself is unlikely to be a target for intervention.…”

Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

“…It was also difficult to conduct the evaluations separately from the influence of other systemic inflammatory diseases. 21,54,55 The target range of teicoplanin concentration has been reported to be 15-30 mg/L of C min , and several loading dose regimens have been evaluated in previous studies. 7,[10][11][12][13] The present study suggests that a higher loading dose (800 mg or 12-15 mg/kg) and dose adjustment based on body size are necessary to obtain this target range at the beginning of teicoplanin administration.…”

FebriDx®: A Rapid Diagnostic Test for Differentiating Bacterial and Viral Aetiologies in Acute Respiratory Infections

“…The FebriDx test is an immunoassay that utilizes simultaneous, qualitative measurement of CRP and MxA in peripheral whole blood [16]. CRP is a non-specific acute-phase protein that serves as a sensitive and early marker of inflammation, tissue injury or infection [20][21][22][23]. CRP levels become markedly elevated in the presence of a clinically significant acute bacterial infection and, as such, CRP measurement can play a role in the diagnosis of such infections; however, CRP is not considered to be sufficiently specific as a marker on its own to differentiate between bacterial and viral infections [20][21][22][23][24][25][26].…”

“…CRP is a non-specific acute-phase protein that serves as a sensitive and early marker of inflammation, tissue injury or infection [20][21][22][23]. CRP levels become markedly elevated in the presence of a clinically significant acute bacterial infection and, as such, CRP measurement can play a role in the diagnosis of such infections; however, CRP is not considered to be sufficiently specific as a marker on its own to differentiate between bacterial and viral infections [20][21][22][23][24][25][26]. MxA is an intracellular GTPase protein that is induced by type I and type III interferons [27] and which serves as a sensitive and specific marker for viral infection [28][29][30][31][32].…”