C-reactive protein, interleukin 6 and lung cancer risk: a meta-analysis

Purpose

Epidemiologic findings are inconsistent concerning the associations between C-reactive protein (CRP), interleukin 6 (IL-6) and lung cancer risk. We conducted a meta-analysis of epidemiologic studies to examine these associations.

Methods

A systematic literature search up to October 2011 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model.

Results

The 10 studies on CRP involved a total of 1918 lung cancer cases. The pooled RR of lung cancer for one unit change in natural logarithm (ln) CRP was 1.28 (95% CI 1.17–1.41). There was no statistically significant heterogeneity among studies (P = 0.116; I² = 36.6%). We also found that CRP was significantly associated with increased risk of lung cancer among men (RR 1.18, 95% CI 1.09–1.28) but not among women. The 5 studies on IL-6 involved a total of 924 lung cancer cases. The pooled RR of lung cancer for one unit change in ln IL-6 was 1.28 (95% CI 0.92–1.79), however, statistically significant heterogeneity was found. After excluding the study contributing most to the heterogeneity, the summary estimate was essentially unchanged.

Conclusion

CRP was associated with increased risk of lung cancer, especially among men. There was no significant association between IL-6 and lung cancer risk.     

C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder: a pilot study

BACKGROUND: it has been reported that psychological stress in humans is associated with a derangement of biological homeostasis. This pilot study aimed to examine the inflammatory response to post-traumatic stress disorder (PTSD) through measurements of the serum levels of the receptor to interleukin 6 (sIL-6r) and C-reactive protein (CRP), in relation to measures of psychological disturbance. METHODS: 15 patients with established PTSD and eight control patients with musculoskeletal injuries were studied at least three months after their index trauma. All completed revised impact of events scale (RIES), Davidson's trauma scale (DTS) and the general health questionnaire (GHQ), and gave blood samples that were assayed for CRP and sIL-6r. Statistical analysis was by the Mann-Whitney U-Wilcoxon rank sum tests. RESULTS: positive relationships were found between sIL-6r and the RIES intrusion score (P=0.026), and between CRP and DTS intrusion scores (P=0.016), GHQ depression (P=0.028), and RIES intrusion (P=0.044) in the case group. DISCUSSION: we have demonstrated a relationship between post-traumatic psychological and biological disturbance, which provides the basis for further research on the effects of psychological disturbance on physical recovery after injury.     

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.     

细菌性肺炎患者IL-6及IL-8及C反应蛋白的测定及其意义

目的探讨白细胞介素6(IL-6)、白细胞介素8(IL-8)和C反应蛋白(CRP)在细菌性肺炎患者中的水平及其临床意义。方法以120例细菌性肺炎患者为试验组,以80例健康人作为对照组;分别抽取对照组及试验组治疗前后的空腹静脉血进行IL-6、IL-8和CRP的检测。结果细菌性肺炎患者中的IL-6及IL-8及CRP均明显高于对照组,差异具有统计学意义(P0.001)。同时与治疗前相比,细菌性肺炎组患者治疗后IL-6及IL-8及CRP水平明显降低,差异具有统计学意义(P0.001),而与对照组相比差异无统计学意义(P0.05)。结论 IL-6及IL-8及CRP在细胞性肺炎患者中的检测有助于患者病情的早期诊断及疗效评估。     

The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.     

High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein

Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1+/-0.03 pg/ml to 2. 0+/-0.5 pg/ml (day 2, P=0.03), IL-1ra from 101+/-21 to 284+/-73 pg/ml (day 2, P=0.01), and CRP from 1.0+/-0.4 to 5.8+/-1.5 micrograms/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0. 5+/-0.2 pg/ml to 2.0+/-0.8 pg/ml (P=0.02), IL-1ra from 118+/-25 to 213+/-28 pg/ml (P=0.02), and CRP from 0.4+/-0.03 to 3.5+/-1.1 micrograms/ml (P=0.03). IL-8 was below the detection limit of the ELISA (<25 pg/ml) in both studies. The increase of IL-6 and IL-1ra in response to high altitude was delayed and preceded the increase of CRP. We conclude that: (1) circulating IL-6, IL-1ra and CRP are upregulated in response to hypobaric hypoxic conditions at high altitude, and (2) the moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence and the kinetics of high altitude-induced cytokines found in this study support the hypothesis that inflammation is involved in the development of HAPO.     

Oral health status,C-reactive protein and mortality--a 10 year follow-up study

Background: Epidemiological studies have reported a strong association between C‐reactive protein (CRP) and cardiovascular diseases (CVD). Elevated CRP levels have been observed both in dentate individuals with chronic dental infections like periodontal disease and in those edentulous. The mechanisms behind these observations, especially the reasons for the elevation of CRP in the edentulous, are poorly understood. The comparative data on the importance of these inflammatory conditions in the oral cavity as causes of elevated CRP levels and CVD risk factors are also limited. Objective: To determine if edentulism is associated with increased levels of CRP and investigate the possible mechanism for this association; and to study the influence of periodontal disease and edentulism on 10‐year mortality. Subjects: Of the 364 subjects aged 76,81, and 86 years in 1990,196 were dentate and 168 edentulous. By December 1999, 179 had died, almost half (n=87) of them due to cardiovascular disease. Results: Significantly more of the edentulous subjects had elevated (>3 mg/L) CRP levels as compared to those with at least 20 teeth (p<0.01). They also had high salivary microbial counts (p<0.05), and more mucosal lesions (p<0.0001) than those with at least 20 teeth. In multivariate analysis, high microbial counts (OR 2.3, CI 1.06‐5.05) and mucosal lesions (OR 2.18, CI 1.03‐4.61) were significantly associated with elevated CRP levels. The risk for all‐cause mortality was non‐significantly elevated among the edentulous (RR 1.48, CI 0.95 – 2.31) and dentate with periodontal disease (RR 1.58, CI 0.96 – 2.61). CVD mortality was significantly higher among the dentate with periodontal disease (RR 1.97, CI 1.01 – 3.85) when compared with dentate without periodontal disease. Conclusion: Among the edentulous, chronic infections like denture‐related mucosal lesions are important determinants of elevated CRP, comparable to periodontal disease in the dentate. Elevated CRP per se and edentulism were not significantly associated with increased mortality. Periodontal disease was, however, still associated with a two‐fold CVD mortality in this very old population.     

Interleukin-6, Age,and Corpus Callosum Integrity

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.     

Interleukin-6 (IL-6) and C-reactive protein (CRP) concentration prior to total nephrectomy are prognostic factors in localized renal cell carcinoma (RCC)

Background

Radical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient.

Aim

The aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC.

Materials and methods

Our prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0.

Results

Statistically significant relationships were found between the concentration of CRP before the operation and OS (p = 0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p = 0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p = 0.0096) and CSS (p = 0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times.

Conclusions

Results of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS.     

C-reactive protein and genetic variants and cognitive decline in old age: the PROSPER study

Background

Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline.

Methods and Findings

Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial, with 5680 participants with a mean age of 75 years, we examined associations of CRP levels and its genetic determinants with cognitive performance and decline over 3.2 years mean follow-up. Higher plasma CRP concentrations were associated with poorer baseline performance on the Stroop test (P = 0.001) and Letter Digit Tests (P<0.001), but not with the immediate and delayed Picture Learning Test (PLT; both P>0.5). In the prospective analyses, higher CRP concentrations associated with increased rate of decline in the immediate PLT (P = 0.016), but not in other cognitive tests (all p>0.11). Adjustment for prevalent cardiovascular risk factors and disease did not change the baseline associations nor associations with cognitive decline during follow-up. Four haplotypes of CRP were used and, compared to the common haplotype, carrierships associated strongly with levels of CRP (all P<0.007). In comparison to strong associations of apolipoprotein E with cognitive measures, associations of CRP haplotypes with such measures were inconsistent.

Conclusion

Plasma CRP concentrations associate with cognitive performance in part through pathways independent of (risk factors for) cardiovascular disease. However, lifelong exposure to higher CRP levels does not associate with poorer cognitive performance in old age. The current data weaken the argument for a causal role of CRP in cognitive performance, but further study is warranted to draw definitive conclusions.     

Viral Interleukin-6: Structure, pathophysiology and strategies of neutralization

Viral Interleukin-6 (vIL-6) is encoded by Human herpes virus 8 (HHV8), also known as Kaposi's sarcoma (KS)-associated herpes virus (KSHV). HHV8 infection is found in patients with KS, primary effusion lymphoma (PEL) and plasma cell-type of multicentric Castleman's disease (MCD), with a high incidence observed in HIV infected individuals. vIL-6 shares about 25% identity with its human counterpart. Human IL-6 (hIL-6) binds to the human IL-6 receptor (hIL-6R) and the hIL-6/hIL-6R complex associates with the signaling receptor subunit gp130. Upon dimerization of gp130 intracellular signaling is initiated. All cells in the body express gp130 but only some cell types express the hIL-6R. Human IL-6 does not stimulate cells, which do not express hIL-6R. However, a naturally occurring soluble form of the hIL-6R (shIL-6R) can bind hIL-6 and the complex of hIL-6/shIL-6R can stimulate cells, which only express gp130 but no hIL-6R. This process, which has been named trans-signaling, leads to a dramatic increase in the spectrum of hIL-6 target cells during inflammation and cancer. vIL-6, in contrast to hIL-6, can directly bind to and activate gp130 without the need of the hIL-6R. Therefore, at least in theory, vIL-6 can stimulate every cell in the human body. This review highlights the properties of vIL-6 regarding structural features, implications for pathophysiology, and strategies of neutralization. Furthermore, mechanisms of activation of gp130 by hIL-6, vIL-6, and by forced dimerization will be discussed.     

Introns, protein syntheses and aging

In the fungus Podospora, a correlation has recently been established between the presence of circular DNA molecules arising from the mitochondrial genome (SEN-DNAs) and the senescence syndrome. Here, I propose a hypothesis which accounts for the initial event which leads to the first SEN-DNA. A molecule in the most frequent situation where the SEN-DNA is an intron which might code for a maturase. This hypothesis is based upon several observations made either in Podospora or in the yeast S. cerevisiae. It assumes that mitochondrially synthesized maturases are unspecific nucleases able to work at the level of RNA and DNA molecules. Their specificity for RNA splicing instead of DNA is given by cytoplasmic proteins. Therefore, if the balance between cytoplasmic and mitochondrial protein syntheses is disturbed in favour of the mitochondrial compartment, the maturase would be accumulated and allowed to splice introns from DNA instead of RNA molecules. This hypothesis can account for aging of higher eucaryotic cells by postulating analogous processes in their nuclear compartment.     

Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass

BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB.     

Enhancing Interleukin-6 and Interleukin-11 receptor cleavage

Proteolytic cleavage of the membrane-bound Interleukin-6 receptor (IL-6R) by the metalloprotease ADAM17 releases an agonistic soluble form of the IL-6R (sIL-6R), which is responsible for the pro-inflammatory trans-signaling branch of the cytokine's activities. This proteolytic step, which is also called ectodomain shedding, is critically regulated by the cleavage site within the IL-6R stalk, because mutations or small deletions within this region are known to render the IL-6R irresponsive towards proteolysis. In the present study, we employed cleavage site profiling data of ADAM17 to generate an IL-6R with increased cleavage susceptibility. Using site-directed mutagenesis, we showed that the non-prime sites P3 and P2 and the prime site P1′ were critical for this increase in proteolysis, whereas other positions within the cleavage site were of minor importance. Insertion of this optimized cleavage site into the stalk of the Interleukin-11 receptor (IL-11R) was not sufficient to enable ADAM17-mediated proteolysis, but transfer of different parts of the IL-6R stalk enabled shedding by ADAM17. These findings shed light on the cleavage site specificities of ADAM17 using a native substrate and reveal further differences in the proteolysis of IL-6R and IL-11R.     

Effect of different training mode on Interleukin-6 (IL-6) and C-reactive protein (CRP) in type 2 diabetes mellitus (T2DM) patients

[Purpose]

This study was carried out to investigate the effects of different training modes on IL-6 and CRP in patients with type 2 diabetes mellitus (T2DM).

[Methods]

The subjects consisted of 16 middle-aged women with type 2 diabetes mellitus (T2DM), all of whom had no other complications. The 16 subjects were randomly assigned to two experimental groups: the circuit training group (CTG, n = 8) and aerobic training group (ATG, n = 8). Based on measured THR (target heart rate) for maximum oxygen consumption rate, the circuit training group (CTG) exercised at 60% intensity, 60 min/day, 5 sets, 3 days/week for 12 weeks. Based on measured THR (target heart rate) for maximum oxygen consumption rate, the aerobic training group (ATG) exercised at 60% intensity (which was increased gradually in weeks 4, 7, and 10) 60 min/day, 3 days/week for 12 weeks.

[Results]

The results are as follows. Significant decreases in the post training values of weight, % Fat, BMI, IL-6 and CRP (p < .05) were observed in the CTG compared to pre-training. However, there were no differences in the physical characteristic and blood inflammatory factors between the groups (ATG & CTG).

[Conclusion]

In conclusion, the results of this study suggest that circuit training (CT) may be considered as an effective training mode for helping to decrease the blood inflammatory factors (IL-6 and CRP) in patients with type 2 diabetes mellitus (T2DM).     

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol–chloroform extraction by the standard method. IL6 −572 G/C, IL12B 1159 C/A, and IL10 –627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 −627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 −572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 −627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 −627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.     

Interleukin-6: structure-function relationships.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.     

C反应蛋白与动脉粥样硬化

人类C反应蛋白 (C reactiveprotein ,CRP)是在感染和组织损伤时血浆浓度快速、急剧升高的主要的急性期蛋白。CRP可以激活补体和加强吞噬细胞的吞噬而起调理作用 ,从而清除入侵机体的病原微生物和损伤、坏死、凋亡的组织细胞 ,在机体的天然免疫过程中发挥重要的保护作用。关于CRP的研究已经有 70多年的历史 ,传统观点认为CRP是一种非特异的炎症标志物 ,但近十年的研究揭示了CRP直接参与了炎症与动脉粥样硬化等心血管疾病 ,并且是心血管疾病最强有力的预示因子与危险因子