scholarly journals Regulation of Inflammatory Reaction in Health and Disease

2021 ◽  
Vol 22 (10) ◽  
pp. 5277
Author(s):  
Massimo Fioranelli ◽  
Maria Grazia Roccia ◽  
Dana Flavin ◽  
Linda Cota
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Inflammatory Reaction ◽  
Low Dose ◽  
Low Grade ◽  
Systems Medicine ◽  
Therapeutic Approaches ◽  
Inflammatory Conditions ◽  
Multistep Process ◽  
Health And Disease

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.

scholarly journals Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2797
Author(s):  
Evangeline Deer ◽  
Lorena M. Amaral ◽  
Nathan Campbell ◽  
Sarah Fitzgerald ◽  
Owen Herrock ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Low Dose ◽  
Perfusion Pressure ◽  
Chronic Inflammatory Response ◽  
Respiration Rates ◽  
Inflammatory Conditions ◽  
Uterine Perfusion ◽  
Placental Ischemia ◽  
New Onset

IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (n = 6) compared to controls (n = 5) (122 ± 5 vs. 102 ± 3 mmHg, p < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, n = 9, p < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia.

Low-Dose Therapy for the Treatment of Low-Grade Chronic Inflammation

2017 ◽  
pp. 27-38 ◽  
Author(s):  
Massimo Fioranelli ◽  
Marco Del Prete ◽  
Jahaira Carolina Aracena ◽  
Maria Grazia Roccia ◽  
Carlo Dal Lin ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Low Dose ◽  
Low Grade ◽  
Dose Therapy

scholarly journals Effect of vitamin A deficiency on the immune response in obesity

2012 ◽  
Vol 71 (2) ◽  
pp. 290-297 ◽  
Author(s):  
Olga P. García
Keyword(s):  
Vitamin A ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Vitamin A Deficiency ◽  
Critical Role ◽  
Fat Deposition ◽  
Cell Mediated Immunity ◽  
Low Grade ◽  
Th1 Response ◽  
Lower Vitamin

Obesity has been associated with low-grade systemic inflammation and with micronutrient deficiencies. Obese individuals have been found to have lower vitamin A levels and lower vitamin A intake compared with normal-weight individuals. Vitamin A plays a major role in the immune function, including innate immunity, cell-mediated immunity and humoral antibody immunity. It has also been recognised recently that vitamin A has important regulatory functions. Vitamin A status has an important effect on the chronic inflammatory response. Vitamin A deficiency increases a T-helper type 1 (Th1) response, elevates levels of pro-inflammatory cytokines, increases the expression of leptin, resistin and uncoupling proteins (UCP) and promotes adipogenesis. The effect of vitamin A deficiency on obesity might be increasing the risk of fat deposition and also the risk of chronic inflammation associated with obesity. Supplementation with vitamin A in vitro and in animal models has been found to reduce concentrations of adipocytokines, such as leptin and resistin. In conclusion, vitamin A deficiency increases a Th1 response in the presence of obesity and thus, increases the inflammatory process involved in chronic inflammation and fat deposition. The metabolism of leptin and other adipocytokines may play a critical role in the effect of vitamin A deficiency in the inflammatory response observed in obesity.

Abstract 1097: Very-low Dose Endotoxemia Induces High Density Lipoprotein Remodeling and Reduces Cholesterol Efflux in the Absence of a Clinical Inflammatory Response

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sean P Heffron ◽  
Nehal N Mehta ◽  
Margarita de la Llera-Moya ◽  
Karen Terembula ◽  
Christine Hinkle ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cholesterol Efflux ◽  
Low Dose ◽  
Clinical Symptoms ◽  
Fold Increase ◽  
Low Grade ◽  
Human Endotoxemia ◽  
Significant Difference ◽  
And Function ◽  
Low Grade Inflammation

Introduction: Chronic low-grade inflammation is thought to induce atherogenic changes in HDL function. Indeed, we have demonstrated HDL particle remodeling during experimental human endotoxemia (3ng/kg). However, this model is associated with marked clinical symptoms, and may not reflect the chronic low-grade inflammation characteristic of insulin resistant atherogenic states. Hypothesis: We hypothesized that very low-dose human endotoxemia (LPS; 0.6ng/kg) induces sub-clinical inflammation causing changes in HDL composition and function, without generating measurable clinical responses. Methods: Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8) were randomized to separate 36-hour inpatient visits (placebo versus intravenous LPS 0.6ng/kg) in a double-masked, placebo-controlled, crossover study. Serial plasma and serum samples were collected for measurement of cytokines, acute phase reactants, lipids and lipoproteins. Ex-vivo 3 H-cholesterol efflux from FU5AH cells (SR-BI model) to the HDL fraction from serum, serially isolated during placebo/endotoxemia, was examined (N=5). Repeated measures ANOVA was applied to the data. Results: There was no significant difference between placebo and LPS in the clinical measures of inflammatory response, including body temperature and heart rate. Relative to placebo, LPS produced a peak 20-fold increase in TNFα (p = 0.01) and a 15-fold increase in CRP (p <0.001). LPS had no effect on levels of HDL cholesterol, apoA-I, apoA-II or apoB lipoproteins. However, endotoxemia was associated with a significant decrease in plasma phospholipids (p = 0.03) and a 7-fold increase in HDL-associated SAA (p <0.001). Further, LPS induced a 40% reduction in cholesterol efflux to HDL by 12 hours post-LPS administration (p = 0.026) which recovered only slightly by 24 hours post-LPS. Conclusions: A very low-dose of endotoxin produces relatively low-grade innate immune responses, without clinical symptoms, but with significant changes in HDL composition and function. This study provides evidence that a modest inflammatory response, consistent with chronic inflammation in atherogenic states in vivo , induces atherogenic changes in HDL.

scholarly journals Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Suzanne H. Bongers ◽  
Na Chen ◽  
Erinke van Grinsven ◽  
Selma van Staveren ◽  
Marwan Hassani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Inflammation ◽  
Peripheral Blood ◽  
Acute Inflammation ◽  
Experimental Endotoxemia ◽  
Inflammatory Conditions ◽  
Treatment Naïve ◽  
Health And Disease ◽  
Kinetics Of

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (&gt;3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.

scholarly journals Effect of Oxidative Stress on Bone Remodeling in Periprosthetic Osteolysis

2021 ◽  
Author(s):  
Emanuela Galliera ◽  
Luca Massaccesi ◽  
Giuseppe Banfi ◽  
Elena De Vecchi ◽  
Vincenza Ragone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Adverse Reactions ◽  
Implant Design ◽  
Low Grade ◽  
Therapeutic Approaches ◽  
Periprosthetic Osteolysis ◽  
Local Inflammatory Response ◽  
Key Factor ◽  
Anti Oxidant

AbstractThe success of implant performance and arthroplasty is based on several factors, including oxidative stress-induced osteolysis. Oxidative stress is a key factor of the inflammatory response. Implant biomaterials can release wear particles which may elicit adverse reactions in patients, such as local inflammatory response leading to tissue damage, which eventually results in loosening of the implant. Wear debris undergo phagocytosis by macrophages, inducing a low-grade chronic inflammation and reactive oxygen species (ROS) production. In addition, ROS can also be directly produced by prosthetic biomaterial oxidation. Overall, ROS amplify the inflammatory response and stimulate both RANKL-induced osteoclastogenesis and osteoblast apoptosis, resulting in bone resorption, leading to periprosthetic osteolysis. Therefore, a growing understanding of the mechanism of oxidative stress-induced periprosthetic osteolysis and anti-oxidant strategies of implant design as well as the addition of anti-oxidant agents will help to improve implants’ performances and therapeutic approaches.

Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats

2020 ◽  
Vol 20 (9) ◽  
pp. 1523-1530
Author(s):  
Murat Dabak ◽  
Durrin O. Dabak ◽  
Tuncay Kuloglu ◽  
Ersoy Baydar ◽  
Hakan Bulut ◽  
...  
Keyword(s):  
Immune Cells ◽  
Low Dose ◽  
Systemic Circulation ◽  
Bilateral Nephrectomy ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Inflammatory Conditions ◽  
Calcium Phosphorus ◽  
25 Hydroxyvitamin D

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

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