Pravastatin attenuates allergic airway inflammation by suppressing antigen sensitisation, interleukin 17 production and antigen presentation in the lung.

BACKGROUND: Statins are widely used to treat hyperlipidaemia. Their immunosuppressive effect has recently been confirmed in various immune mediated disease models. However, relatively few studies have been conducted on allergic inflammation, so the precise mechanisms of their actions against allergies have not been fully clarified. On the other hand, the role of interleukin (IL)17 in immune responses has been recently highlighted, but whether statins affect IL17 production has not been well studied. The effect of pravastatin on allergic airway inflammation in a mouse model was examined to elucidate the mechanism of action, focusing on its effect on IL17 production. METHODS: BALB/c mice were immunised with ovalbumin (OVA) and then challenged with OVA aerosol. Pravastatin was delivered by intraperitoneal injection during either sensitisation or the challenge. RESULTS: When delivered during systemic sensitisation, pravastatin suppressed OVA induced proliferation and production of Th2 type cytokines such as IL5 in spleen cells ex vivo and in vitro. IL17 production was also suppressed. Furthermore, pavastatin delivered during the inhalation of OVA attenuated eosinophilic airway inflammation, OVA specific IgE production in serum and OVA induced IL17 production in the thoracic lymph node. We also found that pravastatin attenuated the antigen presenting capacity of CD11c(+) cells obtained from the OVA challenged lung. CONCLUSION: Pravastatin suppresses the systemic sensitisation to allergen with downregulation of IL17 production. It also suppresses an ongoing immune response in the airway partly by suppressing antigen presentation in the lung. Therefore, statins could be a novel therapeutic option for treatment of asthma.

Longitudinal spin density wave order in a quasi-1D Ising-like quantum antiferromagnet.

From neutron diffraction measurements on a quasi-1D Ising-like Co2+ spin compound BaCo2V2O8, we observed an appearance of a novel type of incommensurate ordering in magnetic fields. This ordering is essentially different from the Néel-type ordering, which is expected for the classical system, and the peculiar spin structure is caused by quantum fluctuation inherent in the quantum spin chain. A Tomonaga-Luttinger liquid nature characteristic of the gapless quantum 1D system is responsible for the realization of the incommensurate ordering.

Novel ordering of an S = 1/2 quasi-1d Ising-like antiferromagnet in magnetic field.

High-field specific heat measurements on BaCo(2)V(2)O(8), which is a good realization of an S=1/2 quasi-one-dimensional (1D) Ising-like antifferomagnet, have been performed in magnetic fields up to 12 T along the chain and at temperature down to 200 mK. We have found a new magnetic ordered state in the field-induced phase above H(c) approximately 3.9 T. We suggest that a novel type of the incommensurate order, which is caused by the quantum effect inherent in the S=1/2 quasi-1D Ising-like antiferromagnet, appears in the field-induced phase.

Field-induced order-disorder transition in antiferromagnetic BaCo(2)V(2)O(8) driven by a softening of spinon excitation.

High field magnetization and ESR measurements on the quasi-one-dimensional (1D) antiferromagnet BaCo(2)V(2)O(8) have been performed in magnetic fields up to 50 T along the chain. The experimental results are explained well in terms of a 1D S=1/2 antiferromagnetic XXZ model in longitudinal fields. We show that the quantum phase transition from the Néel ordered phase to the spin liquid one in the model is responsible for a peculiar order to disorder transition in BaCo(2)V(2)O(8).

In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung.

BACKGROUND: Idiopathic pulmonary fibrosis is a devastating disorder for which there is no effective treatment. Transforming growth factor (TGF)-beta plays a critical role in provoking fibrosis. Interleukin (IL)-10 is a potent immunosuppressive cytokine but its effect on the fibrosing process is unclear. A study was undertaken to examine whether IL-10 affects the production and activation of TGF-beta and thus can attenuate the fibrosis. METHODS: Mice were given an intratracheal injection of bleomycin. On day 1 or 14, IL-10 gene was delivered by rapid intravenous injection of Ringer's solution containing plasmid. Two weeks after the plasmid injection the mice were examined for fibrosis. The effect of IL-10 on TGF-beta production by alveolar macrophages was assessed. RESULTS: Even when delivered during the fibrosing phase, IL-10 gene significantly suppressed the pathological findings, hydroxyproline content, and production of both active and total forms of TGF-beta1 in the lung. Immunohistochemical analyses showed that alveolar macrophages were one of the major sources of TGF-beta1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed the expression of alphaV beta6 integrin, a molecule that plays an important role in TGF-beta activation, on lung epithelial cells. Alveolar macrophages from bleomycin injected mice produced TGF-beta1 spontaneously ex vivo, which was significantly suppressed by treatment of the mice in vivo or by treatment of the explanted macrophages ex vivo with IL-10. CONCLUSION: IL-10 suppresses the production and activation of TGF-beta in the lung and thus attenuates pulmonary fibrosis, even when delivered in the chronic phase.

Vertical density matrix algorithm: a higher-dimensional numerical renormalization scheme based on the tensor product state ansatz.

We present a new algorithm to calculate the thermodynamic quantities of three-dimensional (3D) classical statistical systems, based on the ideas of the tensor product state and the density matrix renormalization group. We represent the maximum-eigenvalue eigenstate of the transfer matrix as the product of local tensors that are iteratively optimized by the use of the "vertical density matrix" formed by cutting the system along the transfer direction. This algorithm, which we call vertical density matrix algorithm (VDMA), is successfully applied to the 3D Ising model. Using the Suzuki-Trotter transformation, we can also apply the VDMA to 2D quantum systems, which we demonstrate for the 2D transverse field Ising model.

Universal asymptotic eigenvalue distribution of density matrices and corner transfer matrices in the thermodynamic limit.

We study the asymptotic behavior of the eigenvalue distribution of the corner transfer matrix (M(CTM)) and the density matrix (M(DM)) in the density-matrix renormalization group. We utilize the relationship M(DM)=M(4)(CTM), which holds for noncritical systems in the thermodynamic limit. We derive the exact and universal asymptotic form of the M(DM) eigenvalue distribution for a class of integrable models in the massive regime. For nonintegrable models, the universal asymptotic form is also verified by numerical renormalization group calculations.