Effect on cellular recruitment and the innate immune response by combining saponin,monophosphoryl lipid-A and Incomplete Freund’s Adjuvant with Leishmania (Viannia) braziliensis antigens for a vaccine formulation

The poor immunogenicity displayed by some antigens has encouraged the development of strategies to improve the immune response and safety of vaccine candidates, resulting in an intense search for substances that potentiate vaccine response. Adjuvants have these properties helping vaccine candidates to induce a strong, durable, and fast immune response. In this study, we evaluated the specific immune response of adjuvants alone, Saponin (SAP), Incomplete Freund’s Adjuvant (IFA) and Monophosphoryl lipid-A SE (MPL-SE®) and in combination with total antigen of L. braziliensis (LB): LBSAP, LBIFA and LBMPL. The specific immune response induced by these compositions demonstrated that they were powerfully immunogenic, increasing cellular infiltration in the skin. Draining lymph nodes cultures showed that LBIFA and LBMPL have higher ability to increase the capacity of APCs to present antigens, with increased frequency of CD11c⁺CD86⁺ cells. SAP, MPL, LBSAP, LBIFA and LBMPL could activate lymphocytes increasing expression of CD69 and CD25. LBSAP group was an excellent inducer of pro-inflammatory cytokines at 24 h. At 48 h, higher cytokines production was observed in IFA, LBIFA, MPL and LBMPL groups. Our data demonstrate that LBSAP and LBMPL are potential formulations to be tested in other experimental models. Also, the data obtained could expand the knowledge about immune response after sensitization and also contribute to the development of safe, immunogenic and effective vaccines.     

Peritoneal dialysis improves lung function in rats with lung injury induced by shock wave

Objective To prove the efficacy of peritoneal dialysis on shock wave-induced acute lung injury of rats, and analyze its mechanisms. Methods Forty-five adult Sprague-Dawley rats were randomly divided into three groups: control group, sham operation (Sham) group and peritoneal dialysis (PD) group. Sham group and PD group did abdominal catheterization before blast injury. The 55 kg shock wave (bst-I) was used to induce lung blast injury. After one hour of blast injury, PD group was given 2.5% peritoneal dialysate 20 ml to stay abdomen, which was released 30 min posted, repeated 12 cycles. After 6 hours of peritoneal dialysis, all of the rats were sacrificed. Partial damaged tissues in lung were used to evaluate the pathomorphologic changes by HE staining, and the remnants were used to measure the lung water content. Lung function was detected by blood gas analyzer and small animal detector from the arterial blood gas. The levels of serum inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) were tested by ELISA. Results The relative integrity of alveolar structure, interstitial edema and inflammatory cell infiltration in PD group were significantly improved than those in control group. The lung water content of PD group was significantly lower than that of control group (P＜0.05). The levels of TNF-α, IL-1β, IL-6 and MCP-1 in serum of PD group were significantly lower than those in control group (all P＜0.05). The blood oxygen saturation, oxygen partial pressure, oxygenation index, vital capacity, functional residual volume and maximum mid-expiratory flow rate in PD group were significantly higher than those in control group (all P＜0.05). Conclusions Through reducing pulmonary edema and inflammatory factors, peritoneal dialysis can improve lung function in shock wave -induced acute lung injury of rats.     

从免疫炎性损伤角度探讨5种清热解毒药物抗流感的机制及其临床意义

目的探讨黄芩、板蓝根、白头翁、虎杖、白花蛇舌草5种清热解毒代表药物抗流感病毒感染所致免疫炎性损伤的作用机制。方法在流感病毒亚洲甲型鼠肺适应株FM1感染小鼠后的不同时相(初期、极期、后期),采用ELISA法,动态观察清热解毒代表药物对小鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、γ干扰素(IFN-γ)5种炎性细胞因子含量的影响。结果黄芩在感染后第3日可显著降低血清TNF-α、IL-1、IL-6含量,并于感染后各时相均可增加IFN-γ含量,感染后第1~5日增加IL-10含量。板蓝根在感染后第3日能显著降低血清TNF-α含量,第3~5日降低IL-6含量,并在感染后第1天升高IL-10含量,在感染后第3~5日能升高IFN-γ含量。白头翁在感染后第3日能明显降低血清TNF-α、IL-1、IL-6含量,同时显著升高IL-10含量。虎杖在感染后第1日可显著升高血清IL-10含量,在感染后第5日升高IFN-γ含量。白花蛇舌草在感染后第3日降低血清IL-6含量,在感染后第5日升高IFN-γ含量。结论黄芩的抗流感作用主要表现在流感病毒感染引起的急性外感热病的极期;板蓝根在流感病毒感染的各个时相均有一定的治疗作用;白头翁在流感病毒感染的极期可抑制炎性损伤;虎杖在感染流感病毒的初期与后期均可减少促炎性细胞因子的分泌;白花蛇舌草在流感病毒感染的极期及后期均可起到一定的抗免疫炎性损伤。各药物均具有抑制炎性损伤、防止多脏器功能衰竭、防止休克、退热和抑制促炎性细胞因子的分泌,调节机体免疫,从而减轻炎症反应的作用。     

不同浓度罗哌卡因复合舒芬太尼分娩镇痛对产妇产间发热的影响

目的研究不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛对产妇产间发热及致热因子的影响。方法适合阴道分娩、自愿要求分娩镇痛的初产妇120例,孕37～41周,年龄20～35岁,ASA I或Ⅱ级,随机分为三组:0.075%罗哌卡因组(A组)、0.1%罗哌卡因组(B组)和0.125%罗哌卡因组(C组),每组40例。宫口扩张至3 cm时实施硬膜外分娩镇痛,A组0.075%罗哌卡因+舒芬太尼0.5μg/ml;B组0.1%罗哌卡因+舒芬太尼0.5μg/ml;C组0.125%罗哌卡因+舒芬太尼0.5μg/ml。记录镇痛后1、2、3、4和5 h、胎儿娩出即刻、分娩后2 h产妇鼓膜温度;分别在镇痛前、胎儿娩出即刻及分娩后2 h采集产妇静脉血,测定血清IL-1β、IL-6、TNF-α浓度;记录产程时间;采用改良Bromage法评定三组产妇在镇痛后1 h及胎儿娩出即刻的运动神经阻滞程度。结果与镇痛前比较,镇痛后5 h及胎儿娩出即刻三组鼓膜温度明显升高,C组发热率明显高于A组和B组(P0.05)。与镇痛前比较,胎儿娩出即刻三组血清IL-1β、IL-6、TNF-α浓度明显升高(P0.05)。C组第二产程和镇痛时间明显长于A组和B组,B组第二产程和镇痛时间明显长于A组(P0.05)。三组运动神经阻滞程度差异无统计学意义。结论不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛均能产生良好的镇痛效果,低浓度罗哌卡因分娩镇痛产妇发热率低,产妇分娩期间发热与致热因子水平升高相关。     

Oligodendrocytes modulate the immune-inflammatory response in EAE via TNFR2 signaling

The pleotropic cytokine tumor necrosis factor (TNF) is involved in the pathophysiology of multiple sclerosis (MS). In various models of MS, including experimental autoimmune encephalomyelitis (EAE), the membrane-bound form of TNF (tmTNF), which signals primarily via TNFR2, mediates protective and reparative effects, whereas the soluble form (solTNF), which signals primarily via TNFR1, promotes pro-inflammatory and detrimental functions. In this study, we investigated the role of TNFR2 expressed in oligodendrocytes in the early phase of EAE pathogenesis. We demonstrated that mice with specific ablation of oligodendroglial TNFR2 displayed early onset and higher peak of motor dysfunction when subjected to EAE, in advance of which accelerated infiltration of immune cells was observed as early as 10 days post EAE induction. The immune cell influx was preceded by microglial activation and increased blood brain barrier permeability. Lack of oligodendroglial TNFR2 accelerated the expression of inflammatory cytokines as well as expression and activation of the inflammasome. Gene expression profiling of oligodendrocytes sorted from the spinal cord 14 days post EAE induction showed robust upregulation of inflammatory genes, some of which were elevated in cells lacking TNFR2 compared to controls. Together, our data demonstrate that oligodendrocytes are directly involved in inflammation and immune modulation in CNS disease and this function is regulated, at least in part, by TNFR2.     

Immunopharmacological intervention for successful neural stem cell therapy: New perspectives in CNS neurogenesis and repair

The pharmacological support and stimulation of endogenous and transplanted neural stem cells (NSCs) is a major challenge in brain repair. Trauma to the central nervous system (CNS) results in a distinct inflammatory response caused by local and infiltrating immune cells. This makes NSC-supported regeneration difficult due to the presence of inhibitory immune factors which are upregulated around the lesion site. The continual and dual role of the neuroinflammatory response leaves it difficult to decipher upon a single modulatory strategy. Therefore, understanding the influence of cytokines upon regulation of NSC self-renewal, proliferation and differentiation is crucial when designing therapies for CNS repair. There is a plethora of partially conflicting data in vitro and in vivo on the role of cytokines in modulating the stem cell niche and the milieu around NSC transplants. This is mainly due to the pleiotropic role of many factors. In order for cell-based therapy to thrive, treatment must be phase-specific to the injury and also be personalized for each patient, i.e. taking age, sex, neuroimmune and endocrine status as well as other key parameters into consideration. In this review, we will summarize the most relevant information concerning interleukin (IL)-1, IL-4, IL-10, IL-15, IFN-γ, the neuropoietic cytokine family and TNF-α in order to extract promising therapeutic approaches for further research. We will focus on the consequences of neuroinflammation on endogenous brain stem cells and the transplantation environment, the effects of the above cytokines on NSCs, as well as immunopharmacological manipulation of the microenvironment for potential therapeutic use.     

Therapeutic effects of conditioned – DPBS from amniotic stem cells on lactating cow mastitis

ObjectiveBovine mastitis results in economic loss due to decrease in milk production. Antibiotic ointments are commonly used for treating. However, residue and anti-microbial resistance warranted attention progressively. Fortunately, stem cell anti-inflammatory properties and paracrine expression of cytokines accelerates wound healing and suppresses inflammatory reactions in mastitis. The objective of this study is to use the conditioned-Dulbecco's pluripotent stem cells (DPBS) from amniotic membrane stem cells (AMSCs) in treating bovine mastitis.Materials and methodsThe cows with mastitis were divided into two groups. In antibiotic control group, the cows were given tetraneomycin ointment. In conditioned-DPBS of AMSCs treatment group, amniotic membrane was collected for AMSCs after delivery. With expression of surface antigen and potential of tri-linage differentiation, AMSCs were injected into mammary glands. Then, milk was sampled every three days to monitor the effect of both treatments. The quality of milk was measured with pH, titratable acidity, free calcium ions and somatic cell count.ResultsOur results demonstrated the Bovine AMSCs expressed CD44, low levels of CD4 and no CD105. Bovine AMSCs demonstrated the differentiation capability in the tri-cell lineages. Mastitis treatment with conditioned-DPBS from AMSCs (experimental group) and conventional antibiotics (control group) showed insignificant difference in pH value and titratable acidity. The level of ionic calcium concentration in the conditioned-DPBS group decreased from 3rd day to 12th day, while the level in the antibiotic group decreased from 0 day to 12th day. The somatic cell number was similar in both groups, which meet the standard of Taiwan milk collection.ConclusionIn conclusion, conditioned-DPBS from bovine AMSCs has the therapeutic potential to treat bovine mastitis and may replace antibiotics therapy in the future.