Passively Administered Pooled Human Immunoglobulins Exert IL-10 Dependent Anti-Inflammatory Effects that Protect against Fatal HSV Encephalitis

HSV-1 is the leading cause of sporadic encephalitis in humans. HSV infection of susceptible 129S6 mice results in fatal encephalitis (HSE) caused by massive inflammatory brainstem lesions comprising monocytes and neutrophils. During infection with pathogenic microorganisms or autoimmune disease, IgGs induce proinflammatory responses and recruit innate effector cells. In contrast, high dose intravenous immunoglobulins (IVIG) are an effective treatment for various autoimmune and inflammatory diseases because of potent anti-inflammatory effects stemming in part from sialylated IgGs (sIgG) present at 1–3% in IVIG. We investigated the ability of IVIG to prevent fatal HSE when given 24 h post infection. We discovered a novel anti-inflammatory pathway mediated by low-dose IVIG that protected 129S6 mice from fatal HSE by modulating CNS inflammation independently of HSV specific antibodies or sIgG. IVIG suppressed CNS infiltration by pathogenic CD11b+ Ly6Chigh monocytes and inhibited their spontaneous degranulation in vitro. FcγRIIb expression was required for IVIG mediated suppression of CNS infiltration by CD45+ Ly6Clow monocytes but not for inhibiting development of Ly6Chigh monocytes. IVIG increased accumulation of T cells in the CNS, and the non-sIgG fraction induced a dramatic expansion of FoxP3+ CD4+ T regulatory cells (Tregs) and FoxP3− ICOS+ CD4+ T cells in peripheral lymphoid organs. Tregs purified from HSV infected IVIG treated, but not control, mice protected adoptively transferred mice from fatal HSE. IL-10, produced by the ICOS+ CD4+ T cells that accumulated in the CNS of IVIG treated, but not control mice, was essential for induction of protective anti-inflammatory responses. Our results significantly enhance understanding of IVIG's anti-inflammatory and immunomodulatory capabilities by revealing a novel sIgG independent anti-inflammatory pathway responsible for induction of regulatory T cells that secrete the immunosuppressive cytokine IL-10 and further reveal the therapeutic potential of IVIG for treating viral induced inflammatory diseases

Multi-Group Reductions of LTE Air Plasma Radiative Transfer in Cylindrical Geometries

Air plasma radiation in Local Thermodynamic Equilibrium (LTE) within cylindrical geometries is studied with an application towards modeling the radiative transfer inside arc-constrictors, a central component of constricted-arc arc jets. A detailed database of spectral absorption coefficients for LTE air is formulated using the NEQAIR code developed at NASA Ames Research Center. The database stores calculated absorption coefficients for 1,051,755 wavelengths between 0.04 m and 200 m over a wide temperature (500K to 15 000K) and pressure (0.1 atm to 10.0 atm) range. The multi-group method for spectral reduction is studied by generating a range of reductions including pure binning and banding reductions from the detailed absorption coefficient database. The accuracy of each reduction is compared to line-by-line calculations for cylindrical temperature profiles resembling typical profiles found in arc-constrictors. It is found that a reduction of only 1000 groups is sufficient to accurately model the LTE air radiation over a large temperature and pressure range. In addition to the reduction comparison, the cylindrical-slab formulation is compared with the finite-volume method for the numerical integration of the radiative flux inside cylinders with varying length. It is determined that cylindrical-slabs can be used to accurately model most arc-constrictors due to their high length to radius ratios

The internal magnetic field in superconducting ferromagnets

We have measured the nonlinear response to the ac magnetic field in the superconducting weak ferromagnet Ru-1222, at different regimes of sample cooling which provides unambiguous evidence of the interplay of the domain structure and the vorticity in the superconducting state. This is {\em direct} proof of coexistence of ferromagnetic and superconductive order parameters in high-$T_c$ ruthenocuprates.Comment: 9 pages, 6 figure