The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

OBJECTIVETo investigate the effect of continuous veno-venous hemofiltration (CVVH) on inflammatory mediators in children with severe hand, foot and mouth disease (HFMD), and to investigate its clinical efficacy.

METHODSA total of 36 children with stage IV HFMD were enrolled and randomly divided into conventional treatment group and CVVH group (n=18 each). The children in the CVVH group were given CVVH for 48 hours in addition to the conventional treatment. The levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and lactic acid in peripheral venous blood, heart rate, blood pressure, and left ventricular ejection fraction were measured before treatment and after 24 and 48 hours of treatment.

RESULTSAfter 24 hours of treatment, the conventional treatment group had a significantly reduced serum IL-2 level (P<0.01), and the CVVH treatment group had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.05). After 48 hours of treatment, both groups had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.01), and the CVVH group had significantly lower levels of these inflammatory factors than the conventional treatment group (P<0.01). After 48 hours of treatment, heart rate, systolic pressure, and blood lactic acid level were significantly reduced, and left ventricular ejection fraction was significantly increased in both groups, and the CVVH group had significantly greater changes in these indices except systolic pressure than the conventional treatment group (P<0.01).

CONCLUSIONSCVVH can effectively eliminate inflammatory factors, reduce heart rate and venous blood lactic acid, and improve heart function in children with severe HFMD.

Child, Preschool ; Cytokines ; blood ; Female ; Hand, Foot and Mouth Disease ; immunology ; physiopathology ; therapy ; Hemodynamics ; Hemofiltration ; Humans ; Infant ; Inflammation Mediators ; blood ; Male ; Ventricular Function, Left

BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 x 109/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.
Adult ; Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Biomarkers, Tumor/*blood ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Hospitals, University ; Humans ; Induction Chemotherapy ; Inflammation Mediators/*blood ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/blood/diagnosis/*drug therapy/immunology/mortality ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Thalidomide/adverse effects/*therapeutic use ; Time Factors ; Transplantation, Autologous ; Treatment Outcome

BACKGROUND/AIMS: Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA. METHODS: A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled. RESULTS: REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance. CONCLUSIONS: We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.
Adult ; Age Factors ; Aged ; Arthritis, Rheumatoid/blood/diagnosis/*metabolism/physiopathology ; Biological Markers/blood ; Body Mass Index ; Case-Control Studies ; Cross-Sectional Studies ; *Energy Metabolism ; Female ; Humans ; Inflammation Mediators/blood ; Middle Aged ; Peptides, Cyclic/immunology ; Predictive Value of Tests ; *Rest ; Rheumatoid Factor/blood ; Severity of Illness Index

Lycii Cortex, a popular herb medicine in traditional Chinese medicine, is used to treat different inflammation-related diseases. The aim of our work is to find the key constituents inhibiting NF-kappaB, a key regulator of inflammation. In the investigations of cell-based in vitro assays of extracts, we found that both ethyl acetate extract and methanol extract of Lycii Cortex inhibited the TNF-alpha-induced activation of NF-kappaB. Through bioassay-guided fractionation, we identified 4 phenolic amides including trans-N-(p-coumaroyl) tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), and dihydro-N-caffeoyltyramine (4). Four phenolic amides showed differently inhibitory activities on TNF-alpha-induced NF-kappaB activation. Trans-N-caffeoyltyramine (3) was identified as the key component with an IC50 of 18.41 micromol x L(-1). It was suggested that the hydroxyl group at C-3 in trans-N-caffeoyltyramine might be a key binding site and its C-7,8-double bond might play an important role on NF-kappaB inhibitory activities as the link of the conjugation of pi electrons leading to a partial planar conformation. It might be inferred that the biological activity of compound 3 is attributed to the structure of Michael reaction acceptor containing alpha, beta-unsaturated ketones and benzene along with hydroxyl group in o-diphenol.
Biological Assay ; Cell Line ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Inflammation Mediators ; antagonists & inhibitors ; immunology ; Lycium ; chemistry ; Molecular Structure ; NF-kappa B ; antagonists & inhibitors ; immunology

OBJECTIVEAntigen-presenting cells such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation during adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Tanshinone II A (TSN) had been shown to decrease the growth of atherosclerotic lesions. We therefore investigated the ability of TSN to inhibit human monocyte-derived DCs and their T-cellstimulatory capacity.

METHODSDCs derived from human monocytes cultured with recombinant human interleukin (IL)-4 and recombinant human granulocyte-macrophage colony-stimulating factor were co-cultured with TSN and lipopolysaccharide for 48 h. Phosphate-buffered saline was used as a negative control. Activation markers and the capacity of DCs for endocytosis were measured by flow cytometry, and proinflammatory cytokines were measured by enzyme-linked immunosorbent assays. DCs were co-cultured with lymphocytes to measure T-cell proliferation and IL-2 secretion by mixed lymphocyte reactions.

RESULTSTSN dose-dependently attenuated DC expression of costimulatory molecules (CD86), and decreased expression of major histocompatibility complex class II (human loukocyte antigen-DR) and adhesion molecules (CD54). Moreover, TSN reduced secretion of the proinflammatory cytokines IL-12 and IL-1 by human DCs, and restored the capacity for endocytosis. Finally, TSN-preincubated DCs showed a reduced capacity to stimulate T-cell proliferation and cytokine secretion.

CONCLUSIONSTSN inhibits DC maturation and decreases the expression of proinflammatory cytokines, while impairing their capacity to stimulate T-cell proliferation and cytokine secretion. These effects may contribute to the influence of TSN on the progression of atherosclerotic lesions.

Antigen-Presenting Cells ; drug effects ; Atherosclerosis ; immunology ; pathology ; B7-2 Antigen ; metabolism ; Cell Membrane ; drug effects ; metabolism ; Cytokines ; secretion ; Dendritic Cells ; drug effects ; immunology ; secretion ; Diterpenes, Abietane ; pharmacology ; Endocytosis ; drug effects ; Flow Cytometry ; Humans ; Immunity, Cellular ; drug effects ; Inflammation Mediators ; metabolism ; Lymphocyte Activation ; drug effects

OBJECTIVETo observe the therapeutic effects of continuous plasma filtration absorption (CPFA) treatment on burn sepsis.

METHODSThirty burn patients with sepsis hospitalized in Beijing Fengtai You'anmen Hospital from July 2009 to October 2012 were treated by CPFA for twice besides routine treatment. The blood samples were collected at five sites (A, B, C, D, and E, respectively) of blood purification equipment before and after CPFA, before and after hemoabsorption, and before hemofiltration. The plasma levels of TNF-α, IL-1β, IL-6, IL-10, interleukin-1 receptor antagonist (IL-1RA), soluble tumor necrosis factor receptor (sTNFR) I , and sTNFR-II from sites A, C, and E were determined with ELISA before CPFA was performed for the first time, and those from sites B and D were determined with ELISA after CPFA was performed for the first time. Plasma levels of the above-mentioned cytokines from sites A and B were determined with ELISA before CPFA and after CPFA was performed for the second time. The data of plasma levels of IL-1βP3, IL-1RA, sTNFR-I, sTNFR-II, and TNF-α before CPFA and after CPFA was performed for the second time were collected for calculation of the ratios of IL-1RA to IL-1β and sTNFR-I plus sTNFR-II to TNF-α. The expression rate of human leukocyte antigen DR (HLA-DR) on the CD14 positive monocytes, acute physiology and chronic health evaluation (APACHE) II score, body temperature, pulse, respiratory rate, and leukocyte count of patients were evaluated or recorded before CPFA and after CPFA was performed for the second time. Patients'condition was observed. Data were processed with paired t test.

RESULTSThe plasma levels of TNF-α, IL-1β, IL-6 and IL-10 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the first time (with t values respectively 7.05, 5.23, 4.73, 2.37, P values below 0.01). After CPFA was performed for the first time, the plasma levels of TNF-α, IL-1β, and IL-6 from site D were significantly lower than those from site C before CPFA was performed for the first time (with t values respectively 5.48, 2. 17, 1.78, P < 0.05 or P <0.01). The plasma levels of all cytokines were close between site B after CPFA was performed for the first time and site E before CPFA was performed for the first time (with t values from 0.04 to 1.05, P values above 0.05). The plasma levels of TNF-α, IL-1β, and IL-6 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the second time (with t values from 1.87 to 5.93, P <0.05 or P <0.01). The ratios of IL-1RA to IL-1β and sTNFR-I plus sTNFR-II to TNF-α, and expression rate of HLA-DR were increased significantly after CPFA was performed for the second time as compared with those before CPFA (with t values from 3.99 to 7. 80, P values below 0.01). APACHE II score after CPFA was performed for the second time was 11 ± 6, which was lower than that before CPFA (22 ± 7, t =4.63, P <0.01). After CPFA was performed for the second time, body temperature, pulse, and respiratory rate of patients were improved (with t values from 1.95 to 3.55, P values below 0.05) , and the leukocyte count was significantly decreased (t =4.36, P <0.01) as compared with those before CPFA. All patients survived and were discharged with length of stay of (27 ± 31) d, and no adverse effects occurred during CPFA treatment.

CONCLUSIONSCPFA, which combines hemoabsorption and hemofiltration, can facilitate the treatment of burn sepsis by decreasing the level of pro-inflammatory cytokines efficiently, alleviating systemic inflammatory response, and improving the immune status.

Adsorption ; Aged ; Biomarkers ; blood ; Burns ; blood ; complications ; immunology ; Cytokines ; blood ; Fluid Therapy ; Hemofiltration ; methods ; Hospitalization ; Humans ; Inflammation Mediators ; blood ; Interleukin 1 Receptor Antagonist Protein ; blood ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Sepsis ; blood ; immunology ; therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.
Apoptosis ; Burns ; immunology ; Caspase 1 ; metabolism ; Cytokines ; Humans ; Inflammasomes ; physiology ; Inflammation Mediators ; immunology ; Interleukin-18 ; immunology ; physiology ; Interleukin-1beta ; immunology ; physiology

BACKGROUND/AIMS: Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. METHODS: We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. RESULTS: Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). CONCLUSIONS: Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.
Adult ; Angina, Unstable/blood/*enzymology/*immunology ; Biological Markers/blood ; C-Reactive Protein/metabolism ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Inflammation Mediators/*blood ; Interleukins/*blood ; Male ; Matrix Metalloproteinase 9/*blood ; Middle Aged ; Myocardial Infarction/blood/*enzymology/*immunology ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1/*blood