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Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. [ABSTRACT FROM AUTHOR]

Abstract: Icaritin is a native compound from Epimedium Genus, a traditional Chinese herbal medicine which is effective in treating asthma, autoimmune diseases and viral infections. In the present paper, the immunosuppressive effects of icaritin were found through in vitro and in vivo studies. Icaritin could dose-dependently inhibit murine CD4+ T cells proliferation stimulated with mitogens or specific antigen ovabumin (OVA). Icaritin at 0.25–25μM could down-regulate T cell activation marker CD25 expression and inhibit IL-2 production. It could also reduce the Th1 cytokine IFN-γ production significantly if the T cells were activated by ConA or anti-CD3; while the inhibition of IL-4 secretion was only seen on anti-CD3 activated T cells treated with low concentrations of icaritin. In vivo study showed that treatment of icaritin at 10mg/kg/day on mice could suppress the immune response with prolonged allograft skin survival. Further study demonstrated that it reduced the alloantigen-induced splenocytes proliferation and Th1/Th2 cytokines. It could also increase NF-AT luciferase activity in Jurkat-NF-AT-luc T cells. The above results suggested that icaritin might be used to treat Th1 dominated immune diseases by interfering T cells activation with mechanism different to CsA. [Copyright &y& Elsevier]

Abstract: Gene therapy mediated by nonviral vectors provides great advantages over conventional drug therapy in inducing immunosuppression after organ transplantation, yet it was rarely reported because T cells are normally difficult to transfect. In this paper, a nonviral vector that effectively transports genes into T cells is developed by attaching a T cell specific ligand, the CD3 single chain antibody (scAbCD3), to the distal ends of poly(ethylene glycol)-grafted polyethylenimine (scAbCD3-PEG-g-PEI). This polymer was first complexed with superparamagnetic iron oxide nanoparticles (SPIONs) and was then used to condense plasmid DNA into nanoparticles with an ideally small size and low cytotoxicity. Based on a reporter gene assay, targeting ligand functionalization of the delivery agent leads to 16 fold of enhancement in the gene transfection level in HB8521 cells, a rat T lymphocyte line. This targeting event in cell culture was successfully imaged by MRI scan. Inspiringly, delivery of a therapeutic gene DGKα with our MRI-visible delivery agent was likewise efficient, resulting in a 43% inhibition in the stimulated proliferation of HB8521 cells as well as a 38% inhibition in the expression of a major functional cytokine interleukin-2 (IL-2), indicating the effective T cell anergy induced by gene therapy. [Copyright &y& Elsevier]

Abstract: In the past years, research on immune regulation has exploded thanks to the re-emergence of T suppressor cells (Ts), now coined as regulatory T cells (Tregs). It has been established that different populations of Tregs exist in the immune system, and the generation, mechanism of suppression and the cellular and molecular targets of Tregs are being unraveled. This will lead to new opportunities for immune intervention to treat autoimmune disease and to achieve clinical transplantation tolerance. The scientific progress in the field of translational medicine was presented at the 7th International Conference on New Trends in Immunosuppression and Immunotherapy in Berlin in February 2006. In this special issue of International Immunopharmacology, several papers submitted to this congress will highlight some of the advances in this burgeoning field of translational medicine. [Copyright &y& Elsevier]

Abstract: Withanolide, coagulin-H (1), was evaluated for its effect on various cellular functions related to immune response including lymphocyte proliferation, and expression of interleukin-2 (IL-2) cytokine, and results were compared with prednisolone (2), a commonly used immune modulating drug. Coagulin-H (1) was found to have a powerful inhibitory effect on lymphocyte proliferation and Th-1 cytokine production. Inhibition of the phytohaemagglutinin (PHA)-activated T-cell proliferation by coagulin-H (1) was observed in a concentration dependant manner. A complete suppression of PHA-activated T-cell was observed at ≥2.5μg/mL concentrations of compound (1) and this suppression activity was similar to that of prednisolone (2). Coagulin-H (1) also significantly inhibited IL-2 production by 80%. The interactions of coagulin-H (1) (a natural inhibitor) and prednisolone (2) (a drug) to IL-2 were also investigated in order to understand the differences in their effects on T-cell responses. This paper also describes the results of molecular docking study on IL-2 inhibition. Docking studies predicted that coagulin-H (1) binds to receptor binding site of IL-2 more effectively than prednisolone (2). Based on the computational and the experimental results, coagulin-H (1) was identified as a potential immunosuppressive candidate. [Copyright &y& Elsevier]

The status of ‘partial’ tolerance to organ allografts versus the status of complete tolerance is the main topic of this paper. Progress made in immunosuppression, particularly by use of various lymphocyte depleting agents for ‘induction therapy’, seems to favor the subsequent development of T cells with suppressor/regulatory properties. The effective deletion of alloreactive T helper and cytotoxic cells in conjunction with the expansion of antigen-specific suppressor (CD8 + CD28 - F0XP3+) and regulatory (CD4 + CD25+ F0XP3+) T cells creates a milieu in which the graft is well tolerated under an ‘umbrella’ of low dosage immunosuppression. The most elective induction treatment is Campath-1H, although ATGAM at high dosage is also widely used. Total lymphoid irradiation (TL1) is another very effective pretreatment strategy in spite of the risks which are associated with it. The induction of ‘partial’ tolerance is a step in the right direction for exploring strategies that may lead to the induction of complete tolerance. It is safe for the patients and can prolong significantly the function of the graft, preventing the onset of chronic rejection. [ABSTRACT FROM AUTHOR]

Immune suppression by Treg cells must be overcome to mount robust and effective anti-pathogen immune responses. A new paper in Immunity from Medzhitov and colleagues shows that IL-1-dependent activation of MyD88 promotes the development of Th1 cells by rendering them impervious to Treg cell-mediated inhibition. [ABSTRACT FROM AUTHOR]