Subcutaneous injection of an immunologically tolerated protein up to 5 days before skin injuries improves wound healing

Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.

Baked egg tolerance: is it possible to predict? / Tolerância aos alimentos assados com ovo: é possível prever quem são esses pacientes?

Abstract Objective: To assess the frequency of baked egg tolerance in IgE-mediated egg allergy patients through the oral food challenge and to assess the tolerance predictability of different skin prick tests, as well as specific serum IgE measurement to egg proteins. Methods: In this cross-sectional study, 42 patients with a diagnosis of egg allergy were submitted to different skin prick tests with egg (in natura, boiled, muffin, ovalbumin, and ovomucoid), and specific IgE to egg white, ovalbumin, and ovomucoid; as well as to the oral food challenge with food containing egg, extensively baked in a wheat matrix. Results: Of the total, 66.6% of patients tolerated the ingestion of egg-containing foods in the oral food challenge. A comparative analysis with positive and negative oral food challenge found no significant differences regarding age, gender, other food allergies, or even specific skin prick tests and IgE values between the groups. Conclusions: The study demonstrated an elevated frequency of baked egg food-tolerant individuals among egg allergy patients. None of the tested markers, skin prick tests, or specific IgE, were shown to be good predictors for identifying baked egg-tolerant patients. The oral food challenge with egg baked in a matrix is central to demonstrate tolerance and the early introduction of baked foods, improving patients' and families' quality of life and nutrient intake.

Resumo Objetivo: Avaliar a frequência de tolerância a alimentos assados com ovo em pacientes com alergia ao ovo mediada por IgE por meio do teste de provocação oral e verificar a capacidade de predição de tolerância ao ovo por meio de teste cutâneo de leitura imediata (Skin Prick Test ou SPT) e de dosagem sérica de IgE específica para componentes do ovo. Métodos: Estudo transversal, 42 pacientes com diagnóstico de alergia ao ovo foram submetidos a SPT com ovo (in natura, cozido, bolinho, ovoalbumina e ovomucoide), IgE específica para clara de ovo, ovoalbumina e ovomucoide e ao teste de provocação oral com alimento com ovo extensamente assado em matriz de trigo. Resultados: Dos pacientes, 66,6% toleraram a ingestão do alimento com ovo durante o teste de provocação oral. Não encontramos diferenças em relação a idade, gênero, outras alergias alimentares ou mesmo entre os valores dos SPT e IgE específica na análise comparativa entre os grupos com teste de provocação oral positivo e teste de provocação oral negativo. Conclusões: Foi demonstrada uma elevada frequência de indivíduos tolerantes a ingestão de alimentos assados com ovo entre os pacientes com alergia a ovo mediada por IgE. Nenhum dos marcadores testados, SPT ou IgE específica, demonstrou ser bom preditor para identificar os pacientes tolerantes. Consideramos que os testes de provocação oral com alimentos com ovo assado sejam fundamentais para a introdução desses assados, melhorar a qualidade de vida e a ingestão de nutrientes dos pacientes e famílias.

Influence of graft weight to recipient liver weight on allogenic rejection after partial liver transplantation / 中华器官移植杂志

Objective To investigate the severity of allogenic rejection after partial liver transplantation (PLTx) with different graft weight to recipient liver weight (GW/RLW).Methods The full-size liver transplantation (group A),GW/RLW ＞33％ PLTx (group B) and GW/RLW ＜ 30％ PLTx (group C) were set up using BN rats and Lewis rats as donors and recipients,respectively.All recipients were observed for 28 days.The Banff RAI grading,survival rate,jaundice and body weight recovery were evaluated to determine the severity of acute allogeneic rejection.Two PLTx groups,group B1 (GW/RLW＞33％) and group C1 (GW/RLW＜30％),were established to assess the mRNA level of IL-2,GranzymeB,Perforin and CD3 48 h and 7 days postoperatively.Additionally,the mRNA level of B7-H1,the ratio of Ki67 + hepatocytes and the liver enzymes were also assessed 7 days postoperatively.Results All recipients in group C died within 22 days postoperatively,presenting with severe lymphocytic infiltration and vascular endothelialitis.All recipients in group A and group B survived until the end of observation time.All recipients in group A survived and presented with a mild lymphocytic infiltration and rare vascular endothelialitis.Group B presented with moderate lymphocytic infiltration and moderate vascular endothelialitis.The Banff RAI grading in group C was significantly higher than that in group A and group B (P ＜ 0.05).In accordance with the result of histology and survival rate,group B and group C presented with earlier jaundice and lower body weight recovery than that of group A (P＜0.05).As compared with group B1,group C1 presented with higher mRNA levels of Perforin,GranzymeB,IL-2 and CD3,higher level of liver enzymes and heavier liver graft weights.Besides,the mRNA level of immunosuppresive molecule B7-H1 in group C1 was lower than that of group B1.However,there was no significant difference in the ratio of Ki67 + hepatocytes between group B1 and group C1.Conclusion The allogenic liver rejection may be enhanced by reducing the GW/RLW.

Effects of Human Adipose-Tissue Derived Stem Cell Infusion on the Immunological Consequences in Skin Allograft Mice / 대한이식학회지

BACKGROUND: Many in vitro experiments have demonstrated the immunosuppressive properties of mesenchymal stem cells (MSCs). However, such properties have not yet been fully established in an in vivo setting. The purpose of this study was to determine immunosuppressive and anti-inflammatory properties of MSCs in a preclinical animal model in order to pave the way for replacement of conventional immunosuppressive therapy. METHODS: Male C57BL/6 mice and male BALB/c mice were chosen as skin graft donors and recipients, respectively. After performance of full-thickness skin transplantation on the back of mice, adipose tissue derived stem cells (1.0x10(6)/0.1 mL) stained with 4, 6-diamidino-2-phenylindole were transplanted into adipose tissue derived stem cell (ASC)-infused mice and phosphate buffered saline (PBS; 0.1 mL) was infused into PBS-infused mice. Immunological properties and graft survival were accessed and compared. RESULTS: The serum levels of proinflammatory interleukin (IL)-6 showed a decrease in ASC-infused mice compared to PBS-infused mice (P<0.005). In addition, interferon-lambda, IL-10, and tumor necrosis factor-alpha mRNA levels in the skin graft showed a decrease in ASC-infused mice, although without statistical significance. In ASC-infused mice, donor specific hyporesponsiveness was identified in a mixed lymphocyte reaction assay at 30 days after transplantation. In addition, ASC-infusion resulted in markedly prolonged skin allograft survival compared with PBS-infusion (P<0.001). CONCLUSIONS: Administration of ASC not only induced anti-inflammation and immunosuppression, but also resulted in prolonged graft survival, suggestive of their potent immunosuppressive properties. Therefore, conduct of further and more exquisite studies will be required in order to determine the role of MSC in the solid organ transplantation field in order to avoid adverse effects and toxicities caused by chemical immunosuppressive regimens.

Reactivación del virus de la hepatitis B secundaria a tratamiento inmunosupresor / Hepatitis B virus reactivation secondary to immunosuppressive treatment

Se presenta el caso de una mujer de 57 años con síntomas dispépticos, con ANAS +, manejada con terapia inmunosupresora y sospecha clínica de LES. Posteriormente presenta ascitis y elevación de las aminotransferasas. Se detecta HBsAg + con carga viral DNA-HBV elevada. Conclusión: Se deben tomar pruebas para hepatitis B antes de iniciar una terapia inmunosupresora. Los corticoesteroides y otros inmunosupresores pueden reactivar el virus de la hepatitis B y producir cuadros clínicos severos que ponen en riesgo la vida del paciente.

Reactivation of hepatitis B virus (HBV) replication in patients undergoing immunosuppressive therapy may precipitate flare ups of chronic HBV infections. We present the case of a 57 year old female who had suffered six weeks of abdominal discomfort, dyspepsia, and joint paint. After three weeks of therapy with prednisolone, methotrexate and chloroquine, the patient developed ascites and increased serum levels of AST and ALT. Chronic hepatitis B infection was confirmed by liver biopsy. Conclusion: Tests for hepatitis B should be conducted before immunosuppressive therapy is begun. Corticosteroids and other immune suppressors can reactivate hepatitis B and produce severe clinical symptoms and can put the patient's life at risk.

Cholera toxin – A foe & a friend.

After De’s pivotal demonstration in 1959 of a diarrhoeogenic exo-enterotoxin in cell-free culture filtrates from Vibrio cholerae (of classical biotype), much insight has been gained about cholera toxin (CT), which is arguably now the best known of all microbial toxins. The subunit structure and function of CT, its receptor (the GM1 ganglioside), and its effects on the cyclic AMP system and on intestinal secretion were defined in the 1970s, and the essential aspects of the genetic organization in the 1980s. Recent findings have generated additional perspectives. The 3D-crystal structure of CT has been established, the CT-encoding operon has been shown to be carried by a non-lytic bacteriophage, and in depth knowledge has been gained on how the bacterium controls CT gene expression in response to cell density and various environmental signals. The mode of entry into target cells and the intracellular transport of CT are becoming clearer. CT has become the prototype enterotoxin and a widely used tool for elucidating important aspects of cell biology and physiology, e.g., cell membrane receptors, the cyclic AMP system, G proteins, as well as normal and pathological ion transport mechanisms. In immunology, CT has emerged as a potent, widely used experimental adjuvant, and the strong oral-mucosal immunogenicity of the non-toxic B-subunit (CTB) has led to the use of CTB as a protective antigen together with killed vibrios in a widely licensed oral cholera vaccine. CTB has also been shown to promote immunological tolerance against certain types of mucosally co-administered antigens, preferably tissue antigens linked to the CTB molecule; this has stimulated research and development to use CTB in this context for treatment of autoimmune and allergic diseases. In summary, in the 50 years after De’s discovery of CT, this molecule has emerged from being the cholera patient’s “foe” to also becoming a highly useful scientist’s “friend”.

Clinical features of severe H1N1 influenza in pregnant women / 中国综合临床

Objective To investigate the clinical characteristics of severe patients with influenza A H1N1. Methods Fifteen prenant pneumonia patients with influenza A H1N1 were selected from November 26 to December 20,2009. Results The average age of all patients was 24 years old,with an average gestational age of 32 weeks. Leukopenia was observed in 13. 3% of IS patients,and lymphopenia in 86. 7%. Data on the ratio of CD4 cells to CD8 cells were available for 12 patients,54. 5% of whom had an abnormal CD4:CD8 ratio(< 1. 4). Ten of the 14 patients(71. 4%)had increased serum lactate dehydrogenase levels,which were above 245 U per liter. Four patients (26. 6%) had elevated creatine kinase levels at admission. 4 cases of 15 patients (26. 7%) had decreased serum potassium levels,which were below 3.5 mmol per liter. Four patients (33. 3%)had C4 levels higer than 36 g per liter,and 4 cases had C3 less than 0.75 g per liter. All 15 patients had radiologically confirmed pneumonia with bilateral patchy alveolar opacities, affecting three or four lung quadrants. Findings on chest radiographs were consistent with the acute respiratory distress syndrome in all patients requiring mechanical ventilation. 4 cases were found a small amount of pleural effusion, of which 1 case was combined a small amount of pericardial effusion. Respiratory distress requiring intubation and mechanical ventilation developed in 9 patients within the first 24 hours after admission, who were all pregnant women. Two of them in the third trimester died, and 7 cases who were timely terminated pregnancy were in stable condition. Conclusions Pandemic influenza A(HIM) may pose an increased risk of severe illness in pregnant women, and it is easy to develop rapidly into adult respiratory distress syndrome. The pregnancy immunological tolerance may be involved in the severe lung injury process of H1N1 influenza pneumonia.

Liver tansplantation in our country should emphasize basic clinical research / 西安交通大学学报(医学版)

Liver transplantation has become an effective and routine treatment for end-stage liver diseases with the employing of new immunosuppressants and surgical techniques. The characteristics of our country's liver transplantation are as follows: the indication for liver transplantation consists mainly of HBV related end-stage liver diseases, patients with liver cancer beyond Milan criteria account for a high rate, and donor origin is not definite. The author thinks that liver transplantation in our country should emphasize basic clinical research, such as prevention of HBV reinfection and tumor relapse after liver transplantation, employing of marginal donor, organ function protection, immunology of liver transplantation, and specific infection around liver transplantation.

Papel das células dendríticas no direcionamento funcional da auto-reatividade celular à HSP60, no sistema humano / The role of human dendritic cells in the functional driving of autoreactivity toward Hsp60, in humans

Nosso objetivo, neste trabalho, foi verificar se a interação das células dendríticas (DCs) com antígenos da Hsp60 induz um efeito sinérgico no direcionamento de uma resposta imune reguladora, no sistema humano. Células dendríticas humanas maduras (mDC) e imaturas (iDC e iDC IL-10) foram geradas, in vitro, a partir de monócitos de 15 de indivíduos saudáveis. Estas células foram caracterizadas quanto à (i) morfologia, (ii) imunofentotipagem, (iii) produção de citocinas e, (iv) capacidade de estimular aloproliferação. Analisamos a auto-reatividade de linfócitos T (LT) dirigida a diferentes DCs (mDC, iDC e iDC IL-10). Na interação de antígenos da Hsp60 com essas diferentes DCs, verificamos: (i) a capacidade de induzir a produção de citocinas pelas DCs e de inibir a sua produção espontânea, (ii) a auto-reatividade de linfócitos T dirigida a esses antígenos (proliferação e produção de citocinas), (iii) a expressão gênica de um painel de moléculas reguladoras (TGFb, receptor de TGF-b, IL-10 e GATA3) e inflamatórias (IFNg, TNF-a e T-bet) em linfócitos, T no contexto de células dendríticas imaturas. As mDC apresentaram expressão de CD83, maior expressão de CD80, e CD86, assim como induziram respostas alogenéicas mais intensas do que as DCs imaturas. Apesar de haver variabilidade na produção de citocinas, apenas as DC imaturas produziram espontaneamente IL-10, e as DCs maduras produziram mais frequentemente IFN-g e TNF-a. Analisando o efeito dos antígenos da Hsp60 sobre a produção de citocinas, observamos tanto indução quanto inibição da produção de IFN-g, TNF-a, IL-4 e IL-10 nos três grupos de DC. Porém, a inibição predominou sobre a produção nos três grupos de DC. A auto-reatividade proliferativa de LT dirigida às diferentes DCs foi mais frequente nas culturas com as DCs maduras (6/10) do que com as DCs imaturas (4/10). Também detectamos produção das citocinas IFN-g, TNF-a, e IL-2 para todos os grupos de células, porém, mais frequentemente na auto-reatividade...

The aim of the present study was to determine whether the interaction of dendritic cells (DCs) with antigens derived from Hsp60 is capable of inducing a synergistic effect in directing a regulatory immune response, using a human system. Human DCs with mature (mDC) and immature (iDC and iDC IL-10) phenotype were generated in vitro from monocytes obtained from 15 healthy subjects. These cells were characterized according to (i) morphology, (ii) expression of surface markers, (iii) cytokine production, and (iv) ability to stimulate alloproliferation. We analyzed the autoreactivity of T lymphocytes (TL) directed against different DC types (mDC, iDC, and iDC IL-10). For the interaction of Hsp60 antigens with these different DCs, we determined: (i) the ability to induce cytokine production by DCs as well as to inhibit their spontaneous production, (ii) the autoreactivity of TL to these antigens (proliferation and cytokine production), and (iii) gene expression levels of a panel of regulatory (TGFb, TGF-b receptor, IL-10, and GATA3) and inflammatory (IFN-g, TNF-a, and T-bet) molecules by TL when stimulated by mDC. mDC expressed CD83 and showed higher levels of CD80 and CD86 and induced stronger allogeneic responses than immature DCs. Although cytokine production varied, only immature DCs spontaneously produced IL- 10, and mature DCs more frequently produced IFN- and TNF-. An analysis of the effects of Hsp60 antigens on cytokine production showed both induction and inhibition of production of IFN-g, TNF-a, IL-4, and IL-10 by the three sets of DCs; however, inhibition predominated over induction in all three DC groups. The proliferative autoreactivity of LT directed towards the different DCs was more frequent in cultures containing mDCs (6/10) than in those containing immature DCs (4/10). We also detected production of IFN-g, TNFa, and IL-2 by all groups of cells; however this was more frequent in the context of autoreactivity against mDCs...

Influence of Oral Antigens on Expression of Costimulatory Molecules CD80/CD86 on Surface of M? / 上海第二医科大学学报

Objective To study the influence of oral antigens on the expression of costimulatory molecules CD80/CD86 on the surface of M and to investigate the genesis of pregnancy immunological tolerance induced by oral antigens through CD80/CD86. Methods Mice of spontaneous abortion(CBA/J?DBA/2) were divided into two groups: immune group and non-immune group.Trophoblast membrane antigen-2(TMA2)or ovum albumin(OVA) was administered orally to the mice in the immune group.Mice of normal pregnancy(CBA/J?BALB/c) were served as controls.The number of CD80/CD86 M of spleen and mesenteric lymph node(MLN) were determined by double-label FCM method. Results In the MLN,CD80 M of non-immune group was increased significantly as compared with that of the control group(P

Evaluation of IL-10 in Renal Allograft Recipients / 上海第二医科大学学报

Objective To study the level of serum IL-10 in renal allgraft recipients with stable renal function,acute rejection,infection and chronic allgraft nephropathy(CAN),and to study the level of serum IL-10 in stable renal function recipients with different postoperative time,different dosage of CsA,different rejective frequency in order to find out the value of IL-10 in the follow-up of out-patients. Methods IL-10 were detected randomly by ELISA technique in 127 renal allgraft recipients during the follow-up,and 20 healthy volunteers were enrolled as controls.Results Level of serum IL-10 in stable renal function group was significantly higher than that in rejection group,CAN group and control group(P

Effects of dendritic cells stimulated with C5b-9 on allogenic lymphocytes / 吉林大学学报(医学版)

Objective To study the effect of dendritic cells(DC) stimulated with C5b-9 on allogenic lymphocytes. Methods DC was stimulated with C5b-9.CD4+ T and CD8+ T cells were isolated by magnetic-activated cell sorting (MACS),and were cocultivated with DC.The maturation markers and cytokine secretion of T cells were analyzed by flow cytometry and ELISA.Results The high pure CD4+ T and CD8+ T cells were separated successfully.After cocultivated with DC,the muturation markers CD25 and CD69 of CD4+ T were up-regulated by 26.31% and 52.73%,and IL-2 and IFN-? of CD4+ T cells were promoted from 126.3 ng?L-1 and 156.7 ng?L-1 to 409.2 ng?L-1 and 471.5 ng?L-1;the levels of IL-10 before and after coculture were 104.3 ng?L-1 and 107.1 ng?L-1.However these markers and cytokine secretion of CD8+ T were not influenced.Conclusion C5b-9 can adjust the function of DC and regulate the immuological response of T cells.

Tolerance for murine skin allograft induced by bone marrow transplantation with the precondition of Tacrolimus (FK506): An experimental study / 中国微创外科杂志

Objective To investigate the feasibility and practicability of the precondition using high-dose of Tacrolimus (FK506) before the bone marrow transplantation (BMT) for macrochimerism specific tolerance. Methods One hundred male C57BL/6 mice and 60 female BALB/C mice were respectively used as donors and recipients of skin transplantation, and another 15 male ICR mice were used as the third germ line to detect the specificity of tolerance. Sixty recipient mice were divided randomly into 5 groups: blank control group, FK506 group, BMT group, experimental group (FK506+BMT) and third party donor control group, with 12 mice in each group. Before the skin transplantation, high-dose abdominal injection of FK506 (3 mg/kg?2 d) was performed in recipient mice. On the transplantation day a bonus of 2?10 7 bone marrow cells were injected through the tail vein. Then a short period of low-dose FK506 (0.5 mg/kg?7 d) was administrated for maintenance treatment. The survival time of skin grafts, reject reaction against the third party skin, and mixed lymphocyte culture (MLC) were observed. The polymerase chain reaction (PCR) was employed for the detection of macrochimerism. Results Routine dose of bone marrow cells infusion or short period of FK506 administration led to neither prolonged survival time of grafts nor the formation of macrochimerism. The skin graft survival time was significantly prolonged in the experimental group (24 0?1 5 d), as compared with the blank control group (9 6?1 1 d), the FK506 group (10 5?1 6 d), the BMT group (10 3?1 5 d), and the third party donor control group (9 8?1 1 d), respectively ( P

Effect of vitamin E on the chronic graft rejection / 肠外与肠内营养

At present, the immunological tolerance in transplantation induced by multi-mechanisms, to inhibit the chronic graft rejection, represents an important trend in the field of transplantation. This review summarizes the new researches about immune and non-immune factors in this field. At the same time, this review also discusses that the high-dose vitamin E, through changing the ratio of Th/Ts in vivo and not improving the level of specific-antibody, regulates the immune system. In addition, the potent antioxidation of vitamin E has advantage to release the oxidate press of tissue and the damage of blood vessels. In the end, the reporter prospects the signification of vitamin E to inhibit the chronic graft rejection and points out the potential questions.