Changes and significance of CD8 + CD28 - regulatory T cells in acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

Correlation between Serum G-CSF Level and Immune Function in Children with Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the occurrence of immune dysfunction in children with aplastic anemia (AA) and the factors that may lead to immune dysfunction, analyze the relationship between the expression of granulocyte colony stimulating factor (G-CSF) and immune dysfunction.@*METHODS@#A total of 34 children with AA treated in our hospital from December 2016 to September 2018 were selected. All the children received immunosuppressive therapy (IST) for 6 months. According to whether the children had immune dysfunction after 6 months of treatment, they were divided into occurrence group and non occurrence group. General information and laboratory indices were compared between the two groups, and serum G-CSF level was tested, the relationship between serum G-CSF level and immune dysfunction in AA children after treatment with IST was observed and analyzed.@*RESULTS@#After treatment with IST for 6 months, 12 cases developed immune dysfunction (35.29%). Serum interferon (IFN)-γ level of the occurrence group was higher but G-CSF level was lower than those of the non occurrence group (P<0.05), while the difference of other baseline data was not statistically significant (P>0.05). Multiple regression analysis showed that overexpression of serum IFN-γ and low expression of G-CSF were both the influencing factors of immune dysfunction in AA children after IST treatment (OR>1, P<0.05). ROC curve was drawn, and the result showed that the area under the curve (AUC) of serum G-CSF level predicted the risk of immune dysfunction after IST was 0.843>0.80, when the index cut-off value was set at 6.614 pg/ml, the predictive value was ideal.@*CONCLUSION@#AA children have a higher risk of immune dysfunction after IST, which may be related to the low expression of serum G-CSF. The detection of serum G-CSF expression can be considered to predict the risk of immune dysfunction in AA children after IST, so as to guide early clinical intervention.

Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study / 世界急诊医学杂志（英文）

@#BACKGROUND: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value. METHODS: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14+ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR). RESULTS: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively. CONCLUSIONS: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

Sepsis and cirrhosis in growing animals: description of a new experimental model and its pathological and immunological reliability

OBJECTIVES: In cirrhotic children, infection events and sepsis are more frequent and more severe due to immune dysfunction. The objectives of the current study were therefore to develop an experimental model of infection and sepsis in cirrhotic weaning growing rats, by the use of bile duct ligation (BDL) and cecal ligation and puncture (CLP). Additionally, the correlation of the clinico-histopathological data and serial cytokine levels in septic cirrhotic and non-cirrhotic animals was studied. METHODS: Young Wistar rats of age 21 days and of weight between 70-90 g were divided into 12 groups according to the surgical procedure performed: sham (sacrificed after 2 or 4 weeks), BDL (sacrificed after 2 or 4 weeks), CLP (2- or 4-week old animals sacrificed after 12 or 24 hours), BDL+CLP (2- or 4-week old animals sacrificed after 12 hours). Histopathological studies and determination of serum levels of cytokines IL-1 beta, IL-10, and TNF-alpha, for studies of systemic infection, were performed. Murine sepsis scores (MSS) based on the clinical aspects just before euthanasia were also included. RESULTS: A transitory increase in IL-1, IL-10, and TNF-alpha levels was observed, with different patterns according to the groups. Two-hit groups tended to present with higher values of serum cytokines and histopathological scores than their septic non-cirrhotic counterparts. There was a correlation between mortality rate and MSS (p<0.0001). CONCLUSION: The model is feasible and may be utilized in studies on liver cirrhosis and infection in growing animals.

Effect of Gandou Decoction on Immune Function of Spleen in TX Mice of Wilson's Disease Model / 中国实验方剂学杂志

Objective: To discuss the effect of Gandou decoction (GDD) on the immune index of spleen in TX mice of Wilson's disease model. Method: The mice were divided into normal group, model group and GDD or tetrathiomolybdate(TM)treatment group, with 20 mice in each group. Each group was fed in various ways for 30 successive days. Normal group:10 normal DL mice were randomly selected and feed normally. Model group:20 TX mice were randomly selected and feed with 2 mL·kg-1·d-1ig saline by gavage twice per day. GDD or TM treatment group:80 TX mice were randomly selected and feed with 2 mL·kg-1·d-1 ig Gandou decoction 22,44,66 g·kg-1 or tetrathiomolybdate by gavage twice per day. ICP-MS was used to compare the expressions of trace elements inside the mice's spleens, flow cytometry was applied to detect the mice T lymphocyte subsets of splenic tissue CD4+, CD8+, CD4+/CD8+, and Western blot was used to detect the expressions of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-8 (IL-8), interleukin-17 (IL-17) and interleukin-18 (IL-18). Result: Flow ICP-MS results showed that GDD can reduce Cu of mice's spleen, flow cytometry results showed that CD4+and CD8+in model group were increased than those in normal group (P+/CD8+was decreased (P+and CD8+in middle and high-dose GDD groups were decreased (P+/CD8+was increased. According to Western blot detection, compared with normal group, the expressions of IL-2, IL-8, IL-17, IL-18, TNF-α and IFN-γ in the model group were increased (Pα, IFN-γ, IL-2, IL-8, IL-17 and IL-18 in the GDD middle and high or TM group were decreased (PPα in the GDD low were decreased (PConclusion: Spleen of TX mice shows the cellular immunity hyperfunction, which is mainly dominated by the negative immunoloregulation. GDD has a certain effect in regulating cellular immunity hyperfunctional state of TX mice, but it's difficult to thoroughly change the negative immune regulation.

Abnormal SCF-C-kit system in IBS-D rat and the correlation between SCF-C-kit system and immune function / 中国药理学通报

Aim To explore the change of stem cell factor-C-kit (SCF-C-kit) system in irritable bowel syn-drome with diarrhea ( IBS-D) and the correlation be-tween SCF-C-kit system and immune dysfunction . Methods Twelve neonatal rats were divided into nor-mal group and model group with six rats in each group . IBS-D rat model was established through three-factor method ( mother-son separation , acetic acid stimulation and constraint ) . Immunohistochemistry was used to observe in situ protein expressions of SCF and C-kit. qPCR was used for mRNA expressions of SCF and C-kit.Correlation between SCF-C-kit system and spleen coefficients , thymus coefficients , TNF-α, IL-8 , IL-10 was analyzed by statistics .Results Compared with normal group , positive rates of SCF and C-kit protein in model group both decreased , and so did mRNA ex-pression .Expression of SCF was negatively correlative with spleen coefficient , TNF-αexpression and IL-8 ex-pression , while positively correlative with IL-10 expres-sion.Expression of C-kit was negatively correlated with thymus coefficient , spleen coefficient and TNF-α. Conclusion SCF-C-kit system of IBS-D is abnormal, which may be related with immune dysfunction .

Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect

ABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping for STAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.

Updated insights into the pathogenesis of sepsis / 医学研究生学报

Sepsis and septic shock are common critical diseases in the ICU, which have a high mortality and seriously affect the patients'' quality of life.The pathogenesis of sepsis is very complicated and involves the changes in the functions of multiple systems and organs.Recently, the investigation into the potential mechanisms underlying the development of sepsis is becoming a hotspot all over the world.The author presents an overview on the advances in the studies of the pathogenesis of sepsis, relating to the imbalance of inflammatory response, immune dysfunction, abnormal blood coagulation, nerve-endocrine-immunity network, mitochondrial function damage, endoplasmic reticulum stress, autophagy, and genetic polymorphism, in order to provide some theoretical evidence for the prevention and treatment of sepsis in clinical practice.

The study of serum complements and proinflammatory cytokines in sepsis rats / 中华危重病急救医学

Objective To observe the changes of serum complements and proinflammatory cytokines in rats with sepsis, and to explore the possible mechanism.Methods 120 healthy male Wistar rats were randomly divided into three groups: normal control group (n = 15), sham operation group (n = 15) and sepsis group [cecum ligation and puncture (CLP) operation,n = 90]. The sepsis rats were sacrificed on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a) and cytokines tumor necrosis factor-α (TNF-α), interleukin (IL-1, IL-6), high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF) were detected by enzyme linked immunosorbent assay (ELISA).Results Compared with normal control group and sham operation group, the levels of serum complements C5, C5a and IL-1β were significantly increased at 24 hours after CLP in sepsis group [C5 (ng/L): 1.60±0.19 vs. 1.04±0.20, 1.09±0.09; C5a (ng/L): 0.20±0.02 vs. 0.18±0.01, 0.18±0.02; IL-1β (ng/L): 700.20±111.41 vs. 475.87±108.96, 592.29±121.57; allP < 0.05]; then the levels of C5, C5a and IL-1β declined, the level of serum C5 were also higher than normal control group at 48 hours and 72 hours after CLP (ng/L: 1.17±0.24, 1.27±0.24 vs. 1.04±0.20, bothP < 0.05). In sepsis group the level of serum TNF-α (ng/L: 51.33±1.96, 51.06±1.64) was lower than that in normal control group (59.53±3.06) and sham operation group (57.91±2.72) at 48 hours and 72 hours (allP < 0.05). There was a time dependent rise of serum HMGB1 in sepsis group, which level was much higher than that in normal control group and sham operation group at 72 hours after CLP (ng/L: 472.21±20.94 vs. 406.00±43.16, 404.41±35.39, bothP < 0.05). There were no significant differences of MIF, and IL-6 level between groups at each time points.Conclusions Complement system led to uncontrolled inflammatory response and immune dysfunction through the release of proinflammatory cytokines and inflammatory mediators, which maybe one of the important mechanism of the pathology of sepsis.

Effects of Shen-Fu Injection () on apoptosis of regulatory T lymphocytes in spleen during post-resuscitation immune dysfunction in a porcine model of cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen.</p><p><b>METHODS</b>After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine (EP) group, and saline (SA) group (8 in each group), which received central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated (sham) group (n=6). After successful return of spontaneous circulation (ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05).</p><p><b>CONCLUSIONS</b>SFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.</p>

Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation.</p><p><b>METHODS</b>Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC.</p><p><b>RESULTS</b>Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups.</p><p><b>CONCLUSIONS</b>SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.</p>

Effect of Valproate exposure-induced autism spectrum disorder model on neuroimmune system of infant mice at early pregnancy / 中华实用儿科临床杂志

Objective To establish the Valproate (VPA) exposure-induced autism spectrum disorder (ASD) model at early pregnancy in rats,and to study the changes of social interaction test and neuroimmune system in autism model rats,and discuss the pathogenic mechanism.Methods Twelve-week-old rats were randomly divided into the non-exposed group (n =10) and the VPA-exposed group (n =10).Their babies were respectively just the normal control group (n =10) and the model group (n =10).The autism-like social behavior was evaluated via the social interaction test.The level of interleukin (IL)-1β,IL-4,IL-6,interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β) in mothers and offspring were detected by using enzyme-linked immunosorbent assay (ELISA).The histopathological damage in brain was observed with immunohistochemical staining.Results The score of social interaction test in the model group [(-163.16 ± 101.92) scores]was lower than that in the normal control group [(132.73 ± 114.63) scores] (t =-6.100,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in VPA-exposed group were higher than those in the non-exposed group (t =5.883,6.394,5.655,5.393,all P ＜ 0.05),while the level of TGF-β was lower than that in the non-exposed group (t =-6.726,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in the model group were higher than those in the normal control group(t =3.058,3.048,6.670,5.486,all P ＜ 0.05),while the level of TGF-β was lower than that in the normal control group (t =-6.516,P ＜ 0.05).The change trend of the level of cytokines in the serum of ASD model rats was similar to the change trend of the level of cytokines in the serum of VPA exposed rats.The result of social interaction test the approach-avoidance score was inversely correlated with the levels of IL-1β and IL-4 (r =-0.802,-0.781,all P ＜ 0.05).The result of immunohistochemical staining showed the expressions of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) in the model group were higher than those in the normal control group.Conclusions The main neuroimmunological pathogenesis mechanism can be explained as follows:at early pregnancy,the maternal cytokines skewing influenced by VPA exposure can make immune activation,induce immune system dysfunction and affect the brain growth and development,which result in autism-like behavior in offspring.

Immune dysfunction and immuno-modulatory therapy on sepsis / 中华实用儿科临床杂志

The relationship between immuno-suppression and poor prognosis of sepsis causes widely concern.Immuno-modulatory therapy is one of the research hotspots in critical medical care.Some studies have shown that to enhance the function of lymphocyte might improve the prognosis of septic patients.This paper will review the immune dysfunction and explore the value of immuno-modulatory therapy in process of sepsis.

The role of regulatory T cells in immune dysfunction during sepsis / 世界急诊医学杂志（英文）

@#BACKGROUND: Although regulatory T cells (Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis. DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and PubMed. Articles on the role of Tregs in immune dysfunction during sepsis were identified. RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function. CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.

Effects of Shenqi Fuzheng injection on immune function in patients with sepsis / 中国中西医结合急救杂志

Objective To observe the effects of Shenqi Fuzheng injection on peripheral blood T lymphocyte subsets, T-cell apoptosis and cytokine in patients with sepsis and approach their significance.Methods Forty patients with sepsis admitted into Department of General Surgery of the General Hospital of Tianjin Medical University were randomly divided into two groups: routine group (20 cases, received routine western medicine treatment) and Shenqi Fuzheng treatment group (20 cases, received routine western medicine treatment and intravenous drip of Shenqi Fuzheng injection 250 mL per day), 7 days as a course of treatment in both groups. On the 1st, 3rd and 7th day after treatment, evaluation of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores was carried out in the two groups. The percentages of peripheral blood T-lymphocyte subsets CD4+, CD8+, CD4+/CD8+ and apoptosis were measured by flow cytometry. Meanwhile, tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-10) levels were detected by enzyme linked immunosorbent assay (ELISA).Results APACHE Ⅱ scores of two groups on the 3rd day were apparently decreased in comparison with those on the 1st day after treatment, and this situation persisted until the 7th day after treatment; meanwhile, the decrease in APACHE Ⅱ score in Shenqi Fuzheng treated group was more notable than that in routine group (10.05±3.71 vs. 13.15±4.65,P 0.05). On the 1st, 3rd and 7th day after treatment, the percentage of CD4+ T cells and CD4+/CD8+ ratio were firstly fallen and then elevated up, the percentage of CD8+ T cells was gradually decreased, and the percentages of CD4+ and CD8+ apoptosis showed a trend of rise up first and then fall in the two groups. On the 7th day after treatment, there were significant differences between Shenqi Fuzheng treated group and routine group in terms of the percentage of CD4+, CD4+/CD8+ ratio and the rate of CD4+ apoptosis [CD4+ T cells: (38.3±4.7)% vs. (35.5±5.5)%, CD4+/CD8+: 1.55±0.29 vs. 1.36±0.27, CD4+ T apoptosis: (11.2±3.8)% vs. (14.1±5.5)%, allP 0.05).Conclusion Shenqi Fuzheng injection can effectively reduce the percentage of CD4+ T cell apoptosis, increase the percentage of CD4+ T cells and CD4+/CD8+ ratio, lower the inflammatory factors, improve the immune function and disease severity in patients with sepsis.

Role of imbalance between transcription factors GATA-3 and T-bet expressions in the pathogenesis of acute lung injury after resuscitation / 中华急诊医学杂志

Objective To study the role of imbalance between transcription factors GATA-3 and T-bet expressions in causing acute lung injury after resuscitation in cardiac arrest model of swine.Methods Mter swine model of electrically induced cardiac arrest was established for 8 minutes,animals were resuscitated to get restoration of spontaneous circulation (ROSC).The swine with ROSC were randomly assigned to be sacrificed at 12 and 24 h after ROSC (n =8 in each group).CD3 +,CD4+ and CD8 + lymphocyte subsets were determined by flow cytometry,and the levels of serum IL-4,TNF-α,and IFN-γ were measured by using ELLSA.The protein levels and expressions of GATA-3/T-bet mRNA were detected in lung tissue by western blotting and quantitative real-time PCR device,respectively.Results Pulmonary function was significantly impaired after ROSC.CD4 + lymphocyte subsets (28.4 ± 2.3) ％,(24.1 ± 1.6) ％ and CD4 +/CD8 + (1.7 ±0.9),(1.5 ± 1.0) were significantly lower in the post-ROSC group compared with the sham-operated group (48.4±2.9)％,(51.1±5.4)％ (2.5±1.3),(2.7±1.1) (P＜0.05) at 12 h and 24 h after ROSC.The levels of serum IL-4 and TNF-α were markedly increased,while IFN-γ and IFN-γ/IL-4 were significantly decreased in the post-ROSC group compared with the sham-operated group (P ＜0.05) at 2-12 h after ROSC.Protein level and expression of GATA-3 mRNA in lung tissue were markedly increased,while those of T-bet were significantly reduced in the post-ROSC group compared with the sham-operated group (P ＜0.05) at 12 and 24 h after ROSC.Conclusions The lung immune dysfunction induced by imbalance between transcription factors GATA-3 mRNA and T-bet mRNA expressions may complicate in the process of post-resuscitation lung injury in a porcine model of cardiac arrest.

Deficiência da STAT5B: uma nova síndrome de insensibilidade ao hormônio de crescimento associada a acometimento imunológico / STAT5B deficiency: a new growth hormone insensitivity syndrome associated to immunological dysfunction

Uma nova apresentação da insensibilidade ao hormônio de crescimento (IGH), causada por mutações em homozigose no gene STAT5B (transdutor de sinal e ativador de transcrição tipo 5B), foi caracterizada nos últimos anos. Sua particularidade é a associação com quadros de disfunção imunológica grave, sendo o mais característico a pneumonite intersticial linfocítica. A presença concomitante de doenças crônicas imunológicas pode fazer com que a baixa estatura seja erroneamente considerada uma consequência do quadro clínico, levando ao subdiagnóstico dessa forma de IGH. O objetivo desta revisão é divulgar o conhecimento atual sobre essa rara patologia, facilitando o reconhecimento de pacientes com IGH secundária a mutações no gene STAT5B em ambulatórios de endocrinologia e de outras especialidades.

A new presentation of growth hormone insensitivity (GHI) caused by homozygous mutations in STAT5B (signal transducer and activator of transcription 5B) gene has been characterized in the last years. Its particularity is the association with severe immune dysfunction, especially with lymphocytic interstitial pneumonitis. This may mislead physicians into considering short stature as secondary to chronic immunological disease and consequently into underdiagnosing this form of GHI. The objective of this review is to propagate current knowledge about this rare pathology, facilitating the diagnosis of patients with GHI due to STAT5B mutations in endocrinology and other specialties clinics.

Aged mice have increased inflammatory monocyte concentration and altered expression of cell-surface functional receptors.

The expression of monocyte cell-surface receptors represents one index of immune dysfunction, which is common with aging. Although mouse models of aging are prevalent, monocyte subset assessment is rare. Our purpose was to compare cell receptor expression on classic (CD115+/Gr-1high) and non-classic (CD115+/Gr-1low) monocytes from 80- or 20-week-old CD-1 mice. Three-colour flow cytometry was used to determine the concentration of monocyte subsets and their respective cell-surface expression of TLR2, TLR4, CD80, CD86, MHC II and CD54. These receptors were selected because they have been previously associated with altered monocyte function. Data were analysed with independent t-tests; significance was set at P<0.05. Old mice had a greater concentration of both classic (258%, P=0.003) and non-classic (70%, P=0.026) monocytes. The classic : non-classic monocyte ratio doubled in old as compared with that in young mice (P=0.006), indicating a pro-inflammatory shift. TLR4 (↓27%, P=0.001) and CD80 (↓37%, P=0.004) were decreased on classic monocytes from old as compared with those from young mice. TLR2 (↑24%, P=0.002) and MHCII (↓21%, P=0.026) were altered on non-classic monocytes from old as compared with those from young mice. The increased classic : non-classic monocyte ratio combined with changes in the cell-surface receptor expression on both monocyte subsets is indicative of immune dysfunction, which may increase age-associated disease risk.

Glutamine as an Immunonutrient

Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.

Quantity change and clinical significance of CD14- CD11b+ CD33+ myeloid-derived suppressor cells in patients with multiple injury / 中华创伤杂志

Objective To explore the quantity change and significance of CD14-/CD11b+/CD33 + myeloid-derived suppressor cells (MDSCs) in patients with multiple injury. Methods Thirtyfour patients with multiple injury and seven healthy volunteers were enrolled in this study. Peripheral blood was collected and the factors of CD14-/CD1 1 b+/ CD33 + were taken as markers of MDSCs. The percentage of MDSCs was determined by flow cytometry (FCM) and serum interleukin-10 and C-reactive protein levels were determined by ELISA to analyze the quantity change and clinical significance of MDSCs. Results The percentage of MDSCs in peripheral blood of healthy volunteers was (1.13 +0. 25) %. At days 1,2, 3 and 7 after injury, the percentage of MDSCs in peripheral blood were (1.20 +0.22) %, (6.44 + 0.35) %, (13.84 ± 2.07) % and (15.60 ± 1.63) % respectively in patients with infection and multiple injury, whereas (1.29 ±0. 30)%, (4.93 +0. 32)%, (5.15 ±0. 21)% and (3.77 ± 0.34) % respectively in patients without infection. The percentages of MDSCs in two groups showed significant differences at days 2, 3 and 7 after trauma (P＜0.05). No correlation was found between MDSCs percentage in peripheral blood and injury severity score, serum interleukin-10 or C reactive protein in patients with multiple injury (P ＞ 0.05). Conclusions The increase of proportion ofMDSCs in peripheral blood correlates with the onset of infection in patients with multiple injury, indicating that the expansion of MDSCs in peripheral blood may play important roles in immune dysfunction after multiple injury.