Phosphocholine-Decorated PPI-Dendrimers Mimic Cell Membrane Phosphocholine Clusters and Tune the Innate Immune Activity of C-Reactive Protein

Abstract Innate immunity has been linked to initiation of Alzheimer’s disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte–macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale [PANSS]) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = −0.161, P = .036). In FEP, normalization of neutrophils (ρ = −0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.

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Zebrafish C-reactive protein isoforms inhibit SVCV replication by blocking autophagy through interactions with cell membrane cholesterol

Scientific Reports ◽

10.1038/s41598-020-57501-0 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Melissa Bello-Perez ◽

Patricia Pereiro ◽

Julio Coll ◽

Beatriz Novoa ◽

Luis Perez ◽

...

Keyword(s):

Cell Membrane ◽

Protein Isoforms ◽

Membrane Cholesterol ◽

C Reactive Protein ◽

Reactive Protein

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Peri-Surgical Inflammatory Profile Associated with Mini-Invasive or Standard Open Lumbar Interbody Fusion Approaches

Journal of Clinical Medicine ◽

10.3390/jcm10143128 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3128

Author(s):

Giovanni Lombardi ◽

Pedro Berjano ◽

Riccardo Cecchinato ◽

Francesco Langella ◽

Silvia Perego ◽

...

Keyword(s):

Interbody Fusion ◽

Venous Blood ◽

Innate Immune ◽

Surgical Approaches ◽

Lumbar Interbody Fusion ◽

C Reactive Protein ◽

Reactive Protein ◽

Hematological Markers ◽

Inflammatory Profile ◽

Definition Of

Background: Different surgical approaches are available for lumbar interbody fusion (LIF) to treat disc degeneration. However, a quantification of their invasiveness is lacking, and the definition of minimally invasive surgery (MIS) has not been biochemically detailed. We aimed at characterizing the inflammatory, hematological, and clinical peri-surgical responses to different LIF techniques. Methods: 68 healthy subjects affected by single-level discopathy (L3 to S1) were addressed to MIS, anterior (ALIF, n = 21) or lateral (LLIF, n = 23), and conventional approaches, transforaminal (TLIF, n = 24), based on the preoperative clinical assessment. Venous blood samples were taken 24 h before the surgery and 24 and 72 h after surgery to assess a wide panel of inflammatory and hematological markers. Results: martial (serum iron and transferrin) and pro-angiogenic profiles (MMP-2, TWEAK) were improved in ALIF and LLIF compared to TLIF, while the acute phase response (C-reactive protein, sCD163) was enhanced in LLIF. Conclusions: MIS procedures (ALIF and LLIF) associated with a reduced incidence of post-operative anemic status, faster recovery, and enhanced pro-angiogenic stimuli compared with TLIF. LLIF associated with an earlier activation of innate immune mechanisms than ALIF and TLIF. The trend of the inflammation markers confirms that the theoretically defined mini-invasive procedures behave as such.

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Effect of Massive Weight Loss on Inflammatory Adipocytokines and the Innate Immune System in Morbidly Obese Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0960 ◽

2006 ◽

Vol 92 (2) ◽

pp. 483-490 ◽

Cited By ~ 112

Author(s):

Melania Manco ◽

J. Manuel Fernandez-Real ◽

Francesco Equitani ◽

Joan Vendrell ◽

Maria Elena Valera Mora ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Massive Weight Loss ◽

Innate Immune ◽

Low Grade ◽

Obese Women ◽

C Reactive Protein ◽

Reactive Protein ◽

Tnf Α ◽

Glucose Sensitivity

Abstract Context: Obesity may be regarded as a low-grade inflammatory state. Objective: The aim of this study was to evaluate changes in pro-inflammatory adipocytokines and the innate immune system, cardiovascular risk, and insulin sensitivity after massive weight loss. Design: This was a longitudinal study. Setting: The study was conducted at Catholic University, Rome. Subjects and Methods: There were 10 normoglucose-tolerant obese women evaluated before and 36 months after bilio-pancreatic diversion (BPD). Glucose sensitivity (M value) was estimated using the euglycemic-hyperinsulinemic clamp. Mannan-binding lectin (MBL), bactericidal/permeability increasing protein (BPI), α-defensins, soluble CD14 receptor (sCD14), C-reactive protein, adiponectin, leptin, visfatin, IL-6, and TNF-α were assayed. Results: After massive weight loss (53% of excess body weight), leptin (P ≤ 0.0001), IL-6 (P ≤ 0.0001), α-defensins (P ≤ 0.001), and C-reactive protein (P ≤ 0.0001) decreased significantly. Adiponectin increased significantly (P ≤ 0.001). Of the nine subjects who lost more than 20% of body mass index, sCD14 (2.87 ± 0.5 to 2.55 ± 0.5; P = 0.016) and visfatin levels (12.20 ± 0.93 to 10.63 ± 1.93 ng/ml; P = 0.045) decreased significantly. No significant changes were observed in TNF-α, BPI, or MBL. Insulin sensitivity more than doubled after BPD (P ≤ 0.0001). sCD14 changes were significantly associated with body mass index (r0 = 0.80; P = 0.003) and M changes (r0 = −0.59; P = 0.03). MBL correlated with insulin sensitivity in obese (r0 = 0.93; P = 0.0001) and post-BPD women (r0 = 0.66; P = 0.038). Adiponectin correlated negatively with cardiovascular risk (r0 = −0.709; P = 0.02) and IL-6 (r0 = −0.634; P = 0.05). Multiple linear regression analysis showed that changes in sCD14 were also significantly related to changes in insulin sensitivity. Conclusions: Surgically induced weight loss is capable of reversing low-grade inflammation, at least partially. The relationships between sCD14, MBL, BPI, and glucose sensitivity, and the role of TNF-α in obesity warrant further investigation.

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Assessment of Inflammasome Activity in Type 2 Diabetes Mellitus and Simple Obesity: Comparative Study

Baghdad Science Journal ◽

10.21123/bsj.10.4.1144-1149 ◽

2013 ◽

Vol 10 (4) ◽

pp. 1144-1149

Author(s):

Baghdad Science Journal

Keyword(s):

Interleukin 1 ◽

Serum Levels ◽

Innate Immune ◽

C Reactive Protein ◽

Reactive Protein ◽

Simple Obesity ◽

High Level ◽

Inflammasome Activity

Inflammasome is a multiprotein oligomer complex which is the precursor procaspase-1 and is a component of the innate immune system so that this study aimed to determine the serum levels of interleukin-1? and 18 in patients with T2D and simple obesity in an attempt to clarify the role of inflammasome in these disorders.Twenty five known cases of T2D, twenty four patients with simple obesity and twenty healthy subjects were randomly recruited from AL-Kindy Teaching Hospital in Baghdad to enroll in this study. All the data about the demographic characteristics and anthropometric measurements were determined in all patients, also the C-reactive protein and serum interleukin (IL)-1? and IL-18 levels were obtained from each patient. The results showed that patients who had positive C-reactive protein (? 6 mg/L) had significant high level of serum 1? and IL-18 levels. Concomitant significant increase in serum levels of IL-1? and IL-18 was observed only in 8% (2 out of 25) of T2D. It concludes that the activity of inflammasome is observed in low percent of T2D and this activity does not related to the obesity.

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Presenting features of COVID-19 in older people: relationships with frailty, inflammation and mortality

10.1101/2020.06.07.20120527 ◽

2020 ◽

Cited By ~ 1

Author(s):

Paul Knopp ◽

Amy Miles ◽

Thomas E Webb ◽

Benjamin C Mcloughlin ◽

Imran Mannan ◽

...

Keyword(s):

Older Adults ◽

Older Individuals ◽

C Reactive Protein ◽

Immune Activity ◽

Neutrophil Lymphocyte Ratio ◽

Reactive Protein ◽

Age Related ◽

Cardinal Symptoms ◽

The Relationship ◽

Age Related Changes

AbstractPurposeTo describe the clinical features of COVID-19 in older adults, and relate these to outcomes.MethodsCohort study of 217 individuals (≥70 years) hospitalised with COVID-19, followed up for allcause mortality. Secondary outcomes included cognitive and physical function at discharge. C-reactive protein and neutrophil: lymphocyte ratio were used as measures of immune activity.ResultsCardinal COVID-19 symptoms (fever, dyspnoea, cough) were common but not universal. Inflammation on hospitalisation was lower in frail older adults. Fever, dyspnoea, delirium and inflammation were associated with mortality. Delirium at presentation was an independent risk factor for cognitive decline at discharge.ConclusionsCOVID-19 may present without cardinal symptoms as well as implicate a possible role for age-related changes in immunity in mediating the relationship between frailty and mortality.Key summary pointsAimTo characterise symptoms, key findings and clinical outcomes in older adults with COVID-19Findings12% of older individuals did not present with classical COVID-19 symptoms, though fever, dyspnoea, delirium and raised inflammation were associated with higher mortality. Compared with fitter older individuals, immune activity was lower in frailer patients.MessageCOVID-19 may present without cardinal symptoms as well as implicate a possible role for age-related changes in immunity in mediating the relationship between frailty and mortality.

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C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response

Journal of Experimental Medicine ◽

10.1084/jem.192.9.1353 ◽

2000 ◽

Vol 192 (9) ◽

pp. 1353-1364 ◽

Cited By ~ 438

Author(s):

Debra Gershov ◽

SunJung Kim ◽

Nathan Brot ◽

Keith B. Elkon

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Factor H ◽

Innate Immune ◽

Classical Pathway ◽

Apoptotic Cells ◽

C Reactive Protein ◽

Complement Components ◽

Reactive Protein ◽

Terminal Complement

C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca2+-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor β. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.

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Serum Calprotectin: An Antimicrobial Peptide as a New Marker For the Diagnosis of Sepsis in Very Low Birth Weight Newborns

Clinical and Developmental Immunology ◽

10.1155/2011/291085 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 37

Author(s):

Gianluca Terrin ◽

Annalisa Passariello ◽

Francesco Manguso ◽

Gennaro Salvia ◽

Luciano Rapacciuolo ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Diagnostic Accuracy ◽

Very Low Birth Weight ◽

Innate Immune ◽

Diagnostic Utility ◽

Healthy Controls ◽

C Reactive Protein ◽

Blood Cell Count ◽

Reactive Protein

To determine the diagnostic utility of serum calprotectin, a mediator of innate immune response against infections, we performed a multicenter study involving newborns with a birth weight<1500 g and a postnatal age>72hours of life. The diagnostic accuracy of serum calprotectin was compared with that of the most commonly used markers of neonatal sepsis (white blood cell count, immature-to-total-neutrophil ratio, platelet count, and C-reactive protein). We found that the serum calprotectin concentration was significantly higher (P<.001) in 62 newborns with confirmed sepsis (3.1±1.0 μg/mL) than in either 29 noninfected subjects (1.1±0.3 μg/ml) or 110 healthy controls (0.91±0.58 μg/ml). The diagnostic accuracy of serum calprotectin was greater (sensitivity 89%, specificity 96%) than that of the traditional markers of sepsis. In conclusion, serum calprotectin is an accurate marker of sepsis in very low birth weight newborns.

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