Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation

BACKGROUND Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METHODS The clinical efficacy of IVIG and IVIG-derived F(ab')2 fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. RESULTS We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab')2 fragments fully recapitulated the clinical efficacy of IVIG. F(ab')2-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab')2 fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund's complete adjuvant which is required for induction of active EAE. CONCLUSIONS Our data indicate that F(ab')2-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS.

Astrotheology: Exoplanets, Christian Concerns, and Human Hopes

Are there planets beyond our solar system? What may appear quite plausible now had only been a hypothesis until about twenty years ago. The search for exoplanets is driven by the interest in the “habitable” ones among them. Could such planets one day in the far future provide resources or even shelter for humankind? Will we find one day a habitable planet that is even inhabited? These kinds of imaginative speculations drive public interest in the subject. Imagining alien intelligent life in the universe is not at all new. When Ted Peters called for establishing the field of “astrotheology,” he was certainly thinking less of historical precedents than of something analogous to the emerging field of astrobiology. Will astrotheology result in the decentering of humanity in cosmic dimensions? One could also conclude that we are alone, at least for all practical purposes.

The Book of Joshua, shadowing forth the fulness of Christian blessing in Christ.

Mode of access: Internet.