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C-reactive protein (CRP) is well-recognized as a sensitive biomarker of inflammation. Association of elevations in plasma/serum CRP level with disease state has received considerable attention, even though CRP is not a specific indicator of a single disease state. Circulating CRP levels have been monitored with a varying degree of success to gauge disease severity or to predict disease progression and outcome. Elevations in CRP level have been implicated as a useful marker to identify patients at risk for cardiovascular disease and certain cancers, and to guide therapy in a context-dependent manner. Since even strong associations do not establish causality, the pathogenic role of CRP has often been over-interpreted. CRP functions as an important modulator of host defense against bacterial infection, tissue injury and autoimmunity. CRP exists in conformationally distinct forms, which exhibit distinct functional properties and help explaining the diverse, often contradictory effects attributed to CRP. In particular, dissociation of native pentameric CRP into its subunits, monomeric CRP, unmasks “hidden” pro-inflammatory activities in pentameric CRP. Here, we review recent advances in CRP targeting strategies, therapeutic lowering of circulating CRP level and development of CRP antagonists, and a conformation change inhibitor in particular. We will also discuss their therapeutic potential in mitigating the deleterious actions attributed to CRP under various pathologies, including cardiovascular, pulmonary and autoimmune diseases and cancer.

Systemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric CRP (pCRP) and the highly pro-inflammatory monomeric isoform (mCRP). The aim of this pilot study was to map the pattern of mCRP distribution in a previously immunologically well-defined colon cancer (CC) cohort and explore possible functional roles of mCRP within the tumor microenvironment (TME). Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 43 stage II and III CC patients, including 20 patients with serum CRP 0-1 mg/L and 23 patients with serum CRP >30 mg/L were immunohistochemically (IHC) stained with a conformation-specific mCRP antibody and selected immune and stromal markers. A digital analysis algorithm was developed for evaluating mCRP distribution within the primary tumors and adjacent normal colon mucosa. mCRP was abundantly present within tumors from patients with high serum CRP (>30 mg/L) diagnostically interpreted as being systemically inflamed, whereas patients with CRP 0-1 mg/L exhibited only modest mCRP positivity (median mCRP per area 5.07‰ (95%CI:1.32-6.85) vs. 0.02‰ (95%CI:0.01-0.04), p<0.001). Similarly, tissue-expressed mCRP correlated strongly with circulating pCRP (Spearman correlation 0.81, p<0.001). Importantly, mCRP was detected exclusively within tumors, whereas adjacent normal colon mucosa showed no mCRP expression. Double IHC staining revealed colocalization of mCRP with endothelial cells and neutrophils. Intriguingly, some tumor cells also colocalized with mCRP, suggesting a direct interaction or mCRP expression by the tumor itself. Our data show that the pro-inflammatory mCRP isoform is expressed in the TME of CC, primarily in patients with high systemic pCRP values. This strengthens the hypothesis that CRP might not only be an inflammatory marker but also an active mediator within tumors.

BackgroundPosttraumatic stress disorder (PTSD) is associated with elevated inflammation and risk for chronic illness, yet few studies have examined inflammatory biomarker outcomes of PTSD interventions. Rapid PTSD symptom reduction has been observed following 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy, which leverages MDMA as a prosocial adjunct to psychotherapy. No studies have evaluated inflammatory biomarker outcomes of MDMA-assisted therapy. This exploratory pilot study examined within-person changes in inflammatory biomarkers during MDMA-assisted group therapy for Veterans with PTSD (www.clinicaltrials.gov, NCT05961527).MethodsBlood plasma samples were collected from 23 Veterans at baseline and end-of-intervention. Hedges’ g effect sizes were calculated for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP). PTSD severity was assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at baseline and 30-day follow-up. Spearman’s rho correlations were calculated among biomarkers, PTSD symptoms, and change scores.ResultsSmall increases were observed in IL-6 (g = 0.24; 95% CI –0.25, 0.72) and CRP (g = 0.23; 95% CI –0.30, 0.74), and a small decrease in TNF-α (g = –0.24; 95% CI –0.69, 0.23). Baseline IL-6 and TNF-α were positively associated with baseline CAPS-5 scores (ρ = 0.45, 0.32). Higher baseline IL-6 weakly predicted symptom improvement (ρ = –0.25), and IL-6 change correlated with symptom change (ρ = 0.41). CRP showed weak negative associations with PTSD symptoms (ρ = –0.26).ConclusionFindings suggest MDMA-assisted therapy may modulate inflammatory biomarkers and highlight biomarker–symptom relationships. Results are preliminary but may inform larger studies.

Eating disorders are important psychiatric conditions with serious implications for physical and mental health. These disorders may be seen in all age groups ages but are more common in adolescents and young adults. Anorexia nervosa, bulimia nervosa, and binge-eating disorder are the main eating disorders. These disorders are triggered by acute stress regarding distorted body image and identified by persistent changes in eating behaviors. Each eating disorder involves different clinical features, but they all share some common risk factors, including genetic predisposition, environmental factors, and psychological triggers. Inflammation is a core mechanism that underlies the pathophysiology of eating disorders. This editorial essay will discuss the evidence linking inflammatory markers to eating disorders' etiology, diagnosis, and treatment.

Objective: To evaluate the prognostic accuracy of the C-reactive protein (CRP)/albumin ratio in predicting severe acute pancreatitis (SAP) and its correlation with clinical complications. Methods: This retrospective observational study included 40 adult patients diagnosed with acute pancreatitis between January and August 2024. Patients were categorized by severity using the Revised Atlanta Classification into moderately severe or severe groups. Laboratory data, clinical characteristics, and imaging findings were compared. Receiver operating characteristic (ROC) analysis with Youden’s Index evaluated the CRP/albumin ratio predictive performance and logistic regression identified independent predictors of SAP. Results: The CRP/albumin ratio was significantly higher in SAP patients (median 5.0 [IQR 0.93–12.62]) compared to non-SAP (1.58 [IQR 0.28–8.6], p = 0.0187). ROC analysis showed an area under the curve (AUC) of 0.809 for the CRP/albumin ratio, superior to CRP alone (AUC 0.479) and comparable to the Ranson score (AUC 0.88). An optimal cut-off value of 4.22 provided 76.9% sensitivity and 85.2% specificity. Multivariable logistic regression identified absence of intestinal transit (p = 0.033) and splenic vein thrombosis (p = 0.026) as independent predictors of SAP. The CRP/albumin ratio correlated significantly with both these complications. Conclusions: The CRP/albumin ratio is a valuable, non-invasive, and readily available prognostic marker for early identification of severe acute pancreatitis. Its predictive accuracy is comparable to established scoring systems and may aid in triage and clinical decision-making.

Abstract Cyclic AMP (cAMP) is a ubiquitous second messenger synthesized by most living organisms. In bacteria, it plays highly diverse roles in metabolism, host colonization, motility, and many other processes important for optimal fitness. The main route of cAMP perception is through transcription factors from the diverse and versatile CRP–FNR protein superfamily. Since the discovery of the very first CRP protein CAP in Escherichia coli more than four decades ago, its homologs have been characterized in both closely related and distant bacterial species. The cAMP-mediated gene activation for carbon catabolism by a CRP protein in the absence of glucose seems to be restricted to E. coli and its close relatives. In other phyla, the regulatory targets are more diverse. In addition to cAMP, cGMP has recently been identified as a ligand of certain CRP proteins. In a CRP dimer, each of the two cyclic nucleotide molecules makes contacts with both protein subunits and effectuates a conformational change that favors DNA binding. Here, we summarize the current knowledge on structural and physiological aspects of E. coli CAP compared with other cAMP- and cGMP-activated transcription factors, and point to emerging trends in metabolic regulation related to lysine modification and membrane association of CRP proteins. This review summarizes the current knowledge on CRP transcription factors allosterically activated by cAMP or cGMP to control highly diverse regulons in a broad range of bacteria.

Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis. We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L). After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82). About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Studies examining post-traumatic stress disorder (PTSD) have either emphasized a relationship between PTSD and a systemically pro-inflammatory state or identified a link between PTSD and chronic disease. The aim of this study was to evaluate the evidence for a relationship between individuals with PTSD and systemic low-grade inflammation that has been proposed to underlie chronic disease development in this population. The authors conducted a systematic review of the literature (January 2006 to April 2017) in accordance with the PRISMA statement in the following four databases: PubMed, MEDLINE, PsycINFO, and SPORTDiscus with Full Text. The search strategy was limited to articles published in peer-reviewed journals and to human studies. Nine studies measuring systemic inflammation and discussing its role in chronic disease development were selected for inclusion in this review. The association between markers of systemic inflammation and PTSD was evaluated by the measurement of a variety of systemic inflammatory markers including acute-phase proteins, complement proteins, pro- and anti-inflammatory cytokines, natural killer cells, and white blood cells. In general, systemic inflammatory biomarkers were elevated across the studies in the PTSD groups. There is evidence that PTSD is underpinned by the presence of a systemic low-grade inflammatory state. This inflammation may be the mechanism associated with increased risk for chronic disease in the PTSD population. From this, future research should focus on interventions that help to reduce inflammation, such as exercise.

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant.