CRP can play both pro-inflammatory and anti-inflammatory roles.
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Animals↗
Biomedical subjects
Irving Kushner
Publications and source records attributed to Irving Kushner.
What does minor elevation of C-reactive protein signify?
Reports of the predictive value of minor elevation of serum C-reactive protein (CRP) levels (between 3 and 10 mg/L) for atherosclerotic events have generated considerable interest, as well as a degree of controversy and confusion. CRP concentrations in this range are found in about one third of the American population. To better understand the mechanisms underlying minor elevation of CRP, we have surveyed its reported associations with a variety of states and conditions. It has become clear that even minimal environmental irritants and inflammatory stimuli elicit a minor CRP response. Minor CRP elevation has been found associated with a number of genetic polymorphisms, with membership in different demographic and socioeconomic groups, with a variety of dietary patterns and with many medical conditions that are not apparently inflammatory. Finally, minor CRP elevation bears negative prognostic implications for many conditions, particularly age-related diseases, and predicts mortality in both diseased and apparently healthy individuals. In sum, minor CRP elevation is associated with a great many diverse conditions, some of which are, or may prove to be, causal. Many of these reported associations imply a mild degree of tissue stress or injury, suggesting the hypothesis that the presence of distressed cells, rather than a resulting inflammatory response, is commonly the stimulus for CRP production.
Biomarkers↗
Improving albumin levels among hemodialysis patients: a community-based randomized controlled trial.
BACKGROUND: Low albumin level is a strong predictor of mortality and morbidity among hemodialysis patients, yet few interventions are available to improve albumin levels. Moreover, the relative importance of nutritional barriers versus inflammation in contributing to hypoalbuminemia is unclear. We sought to determine whether targeting specific nutritional barriers will improve albumin levels. METHODS: We conducted a randomized controlled trial involving 180 patients with baseline albumin levels less than 3.7 g/dL (<37 g/L) at 44 long-term hemodialysis facilities. Study coordinators identified and intervened on specific barriers present among intervention patients, whereas control patients continued to receive the usual care. Barriers targeted included poor nutritional knowledge, poor appetite, help needed with shopping or cooking, low fluid intake, inadequate dialysis dose, depression, difficulty chewing, difficulty swallowing, gastrointestinal symptoms, and acidosis. RESULTS: At baseline, intervention and control patients had similar albumin levels, dietary intakes, levels of inflammatory markers, and numbers of nutritional barriers. After 12 months, intervention patients had greater increases in albumin levels compared with control patients (+0.21 versus +0.06 g/dL [+2.1 versus +0.6 g/L]; P < 0.01), as well as greater increases in energy intake (+4.1 versus -0.6 Kcal/d/kg; P < 0.001) and protein intake (+0.13 versus -0.06 g/d/kg; P < 0.001). The intervention appeared most effective for barriers related to poor nutritional knowledge, help needed with shopping or cooking, and difficulty swallowing. About half the subjects had elevated levels of inflammatory markers, but there was no relationship between change in levels of albumin and inflammatory markers. CONCLUSION: A nutrition intervention tailored to patient-specific barriers resulted in modest improvements in albumin levels regardless of levels of inflammatory markers.
Appetite↗
Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.
OBJECTIVE: To determine the relation between serologic markers of information and clinical characteristics of people with chronic spinal cord injury (SCI). DESIGN: Cross-sectional study. SETTING: Academic medical center SCI outpatient clinic. PARTICIPANTS: Convenience sample of 37 men with chronic SCI and 10 healthy control subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). RESULTS: The following results achieved statistical significance at P less than .05. Asymptomatic chronic SCI patients differed from referent controls with respect to serum CRP levels but not IL-6 or TNF-alpha. In SCI patients, higher levels of CRP correlated negatively with hemoglobin and albumin levels. A longer time since injury correlated with lower TNF-alpha values, whereas higher TNF-alpha levels correlated with higher serum albumin. Pressure ulcers and indwelling urinary catheters were associated with higher mean levels of CRP but not of the cytokines TNF-alpha and IL-6. Intermittent urinary catheterization was associated with lower levels of CRP when compared with other methods of bladder management. CONCLUSIONS: Asymptomatic people with long-term SCI, especially those with indwelling urinary catheters, showed serologic evidence of a systemic inflammatory state. There was no evidence of an elevation in proinflammatory cytokines. Detection of an ongoing systemic inflammatory response in apparently healthy people with indwelling urinary catheters and small skin ulcers further supports the aggressive pursuit of catheter-free voiding options and pressure ulcer healing.
Adult↗
C-reactive Protein.
C-reactive protein (CRP) is a phylogenetically highly conserved plasma protein, with homologs in vertebrates and many invertebrates, that participates in the systemic response to inflammation. Its plasma concentration increases during inflammatory states, a characteristic that has long been employed for clinical purposes. CRP is a pattern recognition molecule, binding to specific molecular configurations that are typically exposed during cell death or found on the surfaces of pathogens. Its rapid increase in synthesis within hours after tissue injury or infection suggests that it contributes to host defense and that it is part of the innate immune response. Recently, an association between minor CRP elevation and future major cardiovascular events has been recognized, leading to the recommendation by the Centers for Disease Control and the American Heart Association that patients at intermediate risk of coronary heart disease might benefit from measurement of CRP. This review will largely focus on our current understanding of the structure of CRP, its ligands, the effector molecules with which it interacts, and its apparent functions.
Animals↗
Transcription factor c-Rel enhances C-reactive protein expression by facilitating the binding of C/EBPbeta to the promoter.
Induction of C-reactive protein (CRP) synthesis in hepatocytes by cytokines occurs at the transcriptional level. In Hep3B cells, the transcription factors C/EBPbeta, STAT3, and Rel p50 have been shown to participate in this process. A C/EBP binding site centered at -53 and an overlapping nonconsensus kappaB site on the promoter are critical for CRP expression. We have previously found that an oligonucleotide containing a kappaB site diminished binding of C/EBPbeta to the C/EBP site, suggesting that unidentified Rel proteins present in Hep3B nuclei facilitate the formation of C/EBPbeta-complexes. The current studies were undertaken to determine which of the five Rel proteins, p50/p65/p52/c-Rel/RelB, play such a role. Mutation of the nonconsensus kappaB site did not abolish binding of C/EBPbeta to its binding site, indicating that this site was not necessary for the formation of C/EBPbeta-complexes. Depletion of Rel proteins from Hep3B nuclei led to decreased formation of C/EBPbeta-complexes on a CRP promoter-derived oligonucleotide that contained only the intact C/EBP binding site but not the nonconsensus kappaB site. This finding indicates that Rel proteins are involved in the binding of C/EBPbeta to its binding site by a kappaB site-independent mechanism. Electrophoretic mobility shift assays (EMSAs) revealed that it was c-Rel that facilitated formation of C/EBPbeta-complexes and that c-Rel bound directly to C/EBPbeta-complexes formed on the C/EBP site. Cotransfection of c-Rel enhanced the induction of CRP promoter-driven luciferase activity and enhanced endogenous CRP expression in cells transfected with C/EBPbeta. We conclude that c-Rel regulates CRP expression without the requirement of binding to a kappaB site, and binds directly to C/EBPbeta to facilitate the binding of C/EBPbeta to the CRP promoter.
Animals↗
Overexpressed nuclear factor-kappaB can participate in endogenous C-reactive protein induction, and enhances the effects of C/EBPbeta and signal transducer and activator of transcription-3.
C-reactive protein (CRP), the prototypical human acute phase protein, is produced primarily by hepatocytes. Its expression is modestly induced by interleukin (IL)-6 in Hep3B cells while IL-1, which alone has no effect, synergistically enhances the effects of IL-6. In previous studies of the proximal CRP promoter, we found that signal transducer and activator of transcription-3 (STAT3) and C/EBPbeta -mediated IL-6-induced transcription and that Rel p50 acted synergistically with C/EBPbeta, in the absence of p65, to enhance CRP transcription. Neither a requirement nor a binding site for the classic nuclear factor (NF)-kappaB heterodimer p50/p65 were found. The current studies were undertaken to determine whether similar novel transcription factor interactions might regulate the endogenous CRP gene. Transiently overexpressed p50 or p65 induced CRP mRNA accumulation in Hep3B cells. The heterodimer p50/p65 was markedly more effective than p50 or p65 homodimers. Co-overexpression of p50 or p65 with C/EBPbeta or STAT3 synergistically enhanced CRP expression. Maximal expression was observed with overexpression of all four transcription factors; comparable effects were observed with IL-1beta treatment of cells overexpressing STAT3 + C/EBPbeta. Data from the Human Genome Project revealed 13 potential kappaB sites in the first 4000 bases of the CRP promoter, only one of which, centred at -2652, bound nuclear p50/p65 heterodimer activated by IL-1beta. Our findings indicate that classical NF-kappaB activation can participate in endogenous CRP induction, and that activated NF-kappaB may synergistically enhance the effects of C/EBPbeta and STAT3. They raise the possibility, not as yet established, that NF-kappaB activation may be responsible for the synergistic effect of IL-1beta on IL-6-induced CRP expression.
C-Reactive Protein↗
An Ethiopian pattern of human adaptation to high-altitude hypoxia.
We describe, in Ethiopia, a third successful pattern of human adaptation to high-altitude hypoxia that contrasts with both the Andean "classic" (erythrocytosis with arterial hypoxemia) and the more recently identified Tibetan (normal venous hemoglobin concentration with arterial hypoxemia) patterns. A field survey of 236 Ethiopian native residents at 3,530 m (11,650 feet), 14-86 years of age, without evidence of iron deficiency, hemoglobinopathy, or chronic inflammation, found an average hemoglobin concentration of 15.9 and 15.0 gdl for males and females, respectively, and an average oxygen saturation of hemoglobin of 95.3%. Thus, Ethiopian highlanders maintain venous hemoglobin concentrations and arterial oxygen saturation within the ranges of sea level populations, despite the unavoidable, universal decrease in the ambient oxygen tension at high altitude.
Adaptation, Physiological↗
C-reactive protein and atherosclerosis.
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Aging↗
Is high-sensitivity C-reactive protein an effective screening test for cardiovascular risk?
We evaluate the suggestion that high-sensitivity C-reactive protein testing be used for risk assessment in the primary prevention of cardiovascular disease, using the criteria proposed by the Guide to Clinical Preventive Services developed by the US Preventive Services Task Force. We conclude that at present, none of the 3 major criteria--accuracy, reliability, and likelihood of beneficial intervention--are satisfied.
C-Reactive Protein↗