Modulation of Soluble Interleukin 2 Receptor (sIL-2R) Levels in Patients with HIVWaldenstrom Macroglobulinemia (HIV-WM) Treated with Biaxin-Pentoxifylline-Dexamethasone Followed by Prednisolone (BPD-Pred)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5214-5214
Author(s):  
Eugene McPherson ◽  
P. Tassy
Keyword(s):  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Serum Levels ◽  
Disease Stage ◽  
Independent Effect ◽  
C Reactive Protein ◽  
Necrosis Factor Alpha ◽  
Reactive Protein

Abstract Serum levels of sIL-2R represents the total amount of activated T-lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organ sites. Most malignant diseases overexpress sIL-2R in comparison to non-malignant controls. Immunomodulatory effect of IL-2 therapy on interferon (IFN), tumor necrosis factor alpha (TNF-a) production, nuclear factor kappa–b (NFkb) in vivo and in vitro and on the expression of sIL-2R in Human Immunodeficiency Virus – Waldenstrom Macroglobulinemia (HIV-WM) patients with IgM is not well defined. We present a 42 year old female with HIV, CD4-343/cu mm, viral load (VL) of >100K (persistently elevated VL), hypercoagulable state, serum viscosity >3 centpoises, IgM level of >1 gram with serum free light chain kappa/lambda ratio elevated as well as IgG and IgA on immunofixation studies. She was treated initially with BPD (Biaxin, Pentoxifylline, Dexamethasone) with partial response and with poor paraprotein parameter response. Her HAART regimen consisted of ritonavir base therapy. When dexamethasone was weaned off and prednisolone therapy started, greater than 50% reduction of paraprotein (IgM) occurred over 4–6 weeks. We measued serum sIL-2R, C-reactive protein (CRP), throughout treatment over 12 weeks. The serum sIL-2R level significantly decreased from 21,513.274 pg/ml to 5,424.779 pg/ml (normal 3,592.9 – 9,734.5 pg/ml). The C-reactive protein normalized and IgM was now 0.211 gram and within normal limits as well as serum viscosity. CONCLUSIONS: The suppression and modulation therapy of CRP gene transcription with manipulation of NFkb/IKKb with ritonavir based HAART and BPD-Pred with normalization of sIL-2R, CRP, and IgM paraprotein in HIV-WM patients may have an independent effect on prognosis and maintenance therapy. Serum sIL-2R levels may serve as a useful marker in evaluating HIV-WM disease, stage for stage and monitoring disease progression.

Interactions between rat C-reactive protein and adult Hymenolepis diminuta

Parasitology ◽  
1997 ◽  
Vol 115 (3) ◽  
pp. 297-302 ◽  
Author(s):  
K. TAYLOR ◽  
D. HOOLE
Keyword(s):  
Regional Distribution ◽  
Serum Levels ◽  
Hymenolepis Diminuta ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Secondary Infections ◽  
Elisa Technique ◽  
Electron Microscopical

Interactions between adult Hymenolepis diminuta and rat C-reactive protein (CRP) were investigated in vivo and in vitro. Using an ELISA technique, serum levels of CRP were monitored in rats infected with 100 cysticercoids. Although infection increased the level of this protein in the early stages of parasitization, the increase was not significant until 35 days post-infection (p.i.). Secondary infections did not enhance the response. When H. diminuta was cultured in the presence of CRP, reduced worm motility and opaque areas were observed and electron microscopical studies revealed shedding of microtriches and lysis of the tegument. Initially, damage was restricted to the strobila which correlated with the regional distribution of phosphorylcholine as visualized using immunofluorescence.

Inhibition of C5a des Arg-induced neutrophil alveolitis in transgenic mice expressing C-reactive protein

1994 ◽  
Vol 266 (6) ◽  
pp. L649-L654 ◽  
Author(s):  
R. M. Heuertz ◽  
D. Xia ◽  
D. Samols ◽  
R. O. Webster
Keyword(s):  
Transgenic Mice ◽  
Elevated Serum ◽  
Neutrophil Infiltration ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Acute Phase Reactant ◽  
C Reactive Protein ◽  
Reactive Protein

C-reactive protein (CRP) is the classic acute phase reactant in man with serum levels elevated up to 1,000-fold after the onset of inflammation. CRP inhibits chemotaxis of complement (C5a)-stimulated neutrophils in vitro and rabbits with elevated serum CRP levels exhibit diminished neutrophil infiltration and vascular permeability in a model of C5a-induced alveolitis. To specifically evaluate the effect of CRP on C5a-induced neutrophil inflammation in vivo, experiments were performed in transgenic mice capable of expressing rabbit CRP in an inducible fashion. After direct instillation of a known inflammatory agent (C5a des Arg) into the airways, transgenic mice with high plasma levels of CRP showed significantly diminished infiltration of neutrophils into bronchoalveolar lavage fluid (BALF) and a significant reduction of BALF total protein levels compared with normal mice. These data indicate that CRP can diminish lung injury by a reduction in neutrophil influx and protein leakage into alveoli following complement-induced inflammation.

Biologic effects of recombinant human interleukin-3 in vivo.

1991 ◽  
Vol 9 (12) ◽  
pp. 2120-2127 ◽  
Author(s):  
A Lindemann ◽  
A Ganser ◽  
F Herrmann ◽  
J Frisch ◽  
G Seipelt ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Serum Levels ◽  
Immunoglobulin M ◽  
Acute Phase Reactants ◽  
Advanced Malignancy ◽  
Interleukin 3 ◽  
Reactive Protein ◽  
Biologic Effects ◽  
In Vivo Effects

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.

scholarly journals Influence of apolipoprotein E genotype and dietary α-tocopherol on redox status and C-reactive protein levels in apolipoprotein E3 and E4 targeted replacement mice

2008 ◽  
Vol 100 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Laia Jofre-Monseny ◽  
Patricia Huebbe ◽  
Inken Stange ◽  
Christine Boesch-Saadatmandi ◽  
Jan Frank ◽  
...  
Keyword(s):  
Apoe Genotype ◽  
Positive Association ◽  
Thiobarbituric Acid ◽  
Redox Status ◽  
C Reactive Protein ◽  
Cvd Risk ◽  
Reactive Protein ◽  
Antioxidant Defence System

The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4 carriers may benefit from α-tocopherol (α-Toc) supplementation. Targeted replacement mice expressing the human apoE3 and apoE4 were fed with a diet poor (0 mg/kg diet) or rich (200 mg/kg diet) in α-Toc for 12 weeks. Neither apoE genotype nor dietary α-Toc exerted any effects on the antioxidant defence system, including glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase activities. In addition, no differences were observed in mitogen-induced lymphocyte proliferation. α-Toc concentrations were modestly higher in plasma and lower in tissues of apoE4 compared with apoE3 mice, with the greatest differences evident in the lung, suggesting that an apoE4 genotype may reduce α-Toc delivery to tissues. A tendency towards increased plasma F2-isoprostanes in apoE4 mice was observed, while liver thiobarbituric acid-reactive substances did not differ between apoE3 and apoE4 mice. In addition, C-reactive protein (CRP) concentrations were reduced in apoE4 mice indicating that this positive effect on CRP may in part negate the increased CVD risk associated with an apoE4 genotype.

scholarly journals C-Reactive Protein Adversely Alters the Protein–Protein Interaction of the Endothelial Isoform of Nitric Oxide Synthase

2010 ◽  
Vol 56 (8) ◽  
pp. 1345-1348 ◽  
Author(s):  
Simona Valleggi ◽  
Sridevi Devaraj ◽  
Mohan R Dasu ◽  
Ishwarlal Jialal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Interactions ◽  
Heat Shock Protein 90 ◽  
C Reactive Protein ◽  
Caveolin 1 ◽  
Reactive Protein ◽  
Oxide Synthase

BACKGROUND C-reactive protein (CRP) inhibits the activity of the endothelial isoform of nitric oxide synthase (eNOS) via uncoupling of the enzyme both in vitro and in vivo. eNOS activity appears to be related in part to its interaction with other cellular proteins, including heat shock protein 90 (Hsp90), caveolin-1, and porin. In this study, we examined the effect of CRP treatment of human aortic endothelial cells (HAECs) on eNOS interaction with caveolin-1, Hsp90, and porin. METHODS We incubated HAECs with CRP (0, 12.5, and 25 mg/L) for 1, 6, or 24 h and assessed the interaction of these proteins with eNOS by immunoprecipitation and western blotting. RESULTS CRP treatment (12.5 and 25 mg/L) of HAECs for 24 h significantly increased eNOS binding to caveolin-1 (40% and 54% increase, respectively; P < 0.05) and decreased binding to Hsp90 (33% and 66% decrease, respectively; P < 0.05). CRP (25 mg/L) also significantly decreased the binding of porin to eNOS (11% decrease, P < 0.05). Similar results were seen when HAECs were treated with CRP for 6 h. CONCLUSIONS These negative protein–protein interactions of eNOS were able to partly explain the CRP-induced decreases in the activity of this critical enzyme, which caused endothelial dysfunction.

Discovery, in-vitro and in-vivo efficacy of an anti-inflammatory small molecule inhibitor of C-reactive protein

2021 ◽  
Author(s):  
Johannes Zeller ◽  
Karen Cheung Tung Shing ◽  
Tracy Nero ◽  
Guy Krippner ◽  
James McFadyen ◽  
...  
Keyword(s):  
Cell Activation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Ischemia ◽  
C Reactive Protein ◽  
Endothelial Cell Activation ◽  
Reactive Protein ◽  
Anti Inflammatory

Abstract C-reactive protein (CRP) is an acute phase protein. We recently identified a novel mechanism that leads to a conformational change from the native, pentameric structure (pCRP) to a pentameric intermediate (pCRP*) and ultimately to the monomeric form, mCRP, both being highly pro-inflammatory. This ‘CRP activation’ is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine (PC) lipid head groups. We designed a low molecular weight pCRP – PC inhibitor, C10M. Binding assays and X-ray crystallography revealed direct, competitive binding of C10M to pCRP, blocking interaction with PC and thereby inhibiting formation of pCRP*/mCRP and their pro-inflammatory effects. The anti-inflammatory potential of C10M was confirmed in-vitro by various measures of leukocyte and endothelial cell activation and in-vivo in rat models of acute ischemia/reperfusion injury and hindlimb transplantation. In conclusion, inhibition of pCRP*/mCRP generation via the PC-mimicking compound C10M represents a promising, potentially broadly applicable anti-inflammatory therapy.

scholarly journals C-Reactive Protein Stimulates Myeloperoxidase Release from Polymorphonuclear Cells and Monocytes: Implications for Acute Coronary Syndromes

2009 ◽  
Vol 55 (2) ◽  
pp. 361-364 ◽  
Author(s):  
Uma Singh ◽  
Sridevi Devaraj ◽  
Ishwarlal Jialal
Keyword(s):  
Plaque Rupture ◽  
Polymorphonuclear Cells ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
Coronary Syndromes ◽  
Human Pmns ◽  
Poor Outcomes

Abstract Background: C-reactive protein (CRP), the prototypic marker of inflammation, is present in atherosclerotic plaques and appears to promote atherogenesis. Also, CRP has been localized to monocytes and tissue macrophages, which are present in the necrotic core of lesions prone to plaque rupture. Leukocyte-derived myeloperoxidase (MPO), primarily hosted in human polymorphonuclear cells (PMNs), has also been shown to be present in human atherosclerotic lesions. Because MPO and CRP concentrations are increased in acute coronary syndrome (ACS) patients and predict poor outcomes, we tested the effect of CRP on MPO release from PMNs and monocytes. Methods: We treated human PMNs and monocytes with CRP (25 and 50 mg/L for 6 h) and measured MPO release as total mass and activity in culture supernatants. We also measured nitro-tyrosinylation (NO2-Tyr) of LDL as an indicator of biological activity of CRP-mediated MPO release. Furthermore, we explored the effect of human CRP on MPO release in the rat sterile pouch model. Results: CRP treatment significantly increased release of MPO (both mass and activity) from human PMNs as well as monocytes (P < 0.05) and caused NO2-Tyr of LDL. Human CRP injection in rats resulted in increased concentrations of MPO in pouch exudates (P < 0.05), thus confirming our in vitro data. Conclusions: CRP stimulates MPO release both in vitro and in vivo, providing further cogent data for the proinflammatory effect of CRP. These results might further support the role of CRP in ACS.

scholarly journals C-Reactive Protein Induces Release of Both Endothelial Microparticles and Circulating Endothelial Cells In Vitro and In Vivo: Further Evidence of Endothelial Dysfunction

2011 ◽  
Vol 57 (12) ◽  
pp. 1757-1761 ◽  
Author(s):  
Sridevi Devaraj ◽  
Pappanaicken R Kumaresan ◽  
Ishwarlal Jialal
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Oxidized Ldl ◽  
Circulating Endothelial Cells ◽  
Early Event ◽  
C Reactive Protein ◽  
Endothelial Microparticles ◽  
Reactive Protein

BACKGROUND Inflammation is pivotal in atherosclerosis. A key early event in atherosclerosis is endothelial dysfunction. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a risk marker for cardiovascular disease, and there is mounting evidence to support its role in atherothrombosis. CRP has been shown to promote endothelial dysfunction both in vitro and in vivo. Emerging biomarkers of endothelial dysfunction include circulating endothelial cells (CECs) and endothelial microparticles (EMPs). However, there is a paucity of data examining the effect of CRP on CEC and EMP production in vitro and in vivo. METHODS In this report, we treated human aortic endothelial cells (HAECs) with increasing concentrations of CRP (0–50 μg/mL) or boiled CRP. We counted CECs and EMPs by flow cytometry. RESULTS Although CRP treatment resulted in a significant increase in release of both CECs and EMPs, boiled CRP failed to have an effect. Pretreatment of HAECs with sepiapterin or diethylenetriamine NONOate, both of which preserve nitric oxide (NO), resulted in attenuation of CRP's effects on CECs and EMPs. CD32 and CD64 blocking antibodies but not CD16 antibody or lectin-like oxidized LDL receptor 1 small interfering RNA (LOX-1 siRNA) prevented CRP-induced production of CECs and EMPs. Furthermore, delivery of human CRP to Wistar rats compared with human serum albumin resulted in significantly increased CECs and EMPs, corroborating the in vitro findings. CONCLUSIONS We provide novel data that CRP, via NO deficiency, promotes endothelial dysfunction by inducing release of CECs and EMPs, which are biomarkers of endothelial dysfunction.

scholarly journals Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A264-A265
Author(s):  
Kosuke Oka ◽  
Jo Araki ◽  
Koichiro Yamamoto ◽  
Yoshihisa Hanayama ◽  
Kazuki Tokumasu ◽  
...  
Keyword(s):  
General Practice ◽  
Bacterial Infection ◽  
Clinical Setting ◽  
Inflammatory Markers ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Diagnostic Process ◽  
Individual Treatment ◽  
C Reactive Protein ◽  
Reactive Protein

Abstract Various laboratory markers are utilized in general practice to detect inflammation, and procalcitonin (PCT) has also been routinely measured in many patients as a marker of bacterial infection and sepsis. An increase in PCT starts before an increase in C-reactive protein (CRP), and PCT level is useful not only for the diagnosis of bacterial infection, sepsis, as an indicator of the severity and prognosis of systemic inflammatory diseases, and is also useful for determination of the response to individual treatment. PCT is a precursor of calcitonin and PCT is not produced in a healthy state but is produced by various tissues in septic conditions. Since there are many patients with elevated levels of PCT due to nonbacterial causes, the levels of serum PCT have been apt to be used for a marker for the early detection of not only bacterial infection but also many inflammatory and/or febrile disorders including fever of unknown origin (FUO) in the clinical setting of general medicine. Here we attempted to clarify the differences and similarities of inflammatory markers for a clinical setting. We retrospectively reviewed 359 patients in whom serum PCT had been measured. According to our earlier study, the patients were categorized into 7 groups: bacterial, non-bacterial infection, non-specific inflammation, neoplasm, connective tissue disease (CTD), drug-induced diseases, and unidentified causes. Data for 332 PCT-positive cases including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), CTD (8.4%), and non-bacterial infection (7.2%) were used for analysis. Serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). Of note, serum PCT level was positively correlated with serum levels of C-reactive protein (R2=0.39), soluble interleukin-2 receptor (sIL-2R; R2=0.48), and ferritin, plasma level of D-dimer level and white blood cell count, whereas it was negatively correlated with serum albumin level (R2=0.27), hemoglobin concentration and platelet count. The result of the strongly positive correlation with serum level of sIL-2R suggested that an increased serum PCT level may indicate not only an inflammatory state but also a neoplastic state such as malignant lymphomas in the diagnostic process of various inflammatory disorders in a clinical setting of general practice for diagnosing febrile conditions.

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