Neurotropin improves the apoptotic thymic defects of New Zealand Black mice

Y. Takeoka, N. Taguchi, M. Naiki, A. A. Ansari, M. Eric Gershwin

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Abstract

New Zealand Black (NZB) mice serve as a model of human systemic lupus erythematosus. Both humans and mice with systemic lupus erythematosus share many clinical and pathologic abnormalities. These includes the finding that both have histologic abnormalities of the thymic microenvironment, including an irregular shape of medullary epithelial clusters and a diffuse corticoepithelial network. It is believed that these abnormalities of the thymic microarchitecture contribute to abnormalities associated with positive and negative selection, the latter being molecules by apoptosis. Previous work has demonstrated that the administration of neurotropin, a unique nonprotein extract, isolated from the inflamed dermis of rabbits inoculated with vaccinia virus, has beneficial effects in murine lupus. The present study was carried out in an effort to determine whether the beneficial effects of neurotropin on immune lupus are mediated by neurotropin's ability to modulate thymic cell apoptosis. The ability of neurotropin to modulate the induction of apoptosis either by in vivo administration of lipopolysaccharides or by in vitro addition of dexamethasone to thymocyte cultures was therefore studied. Interestingly, neurotropin significantly improved the abnormalities of lipopolysaccharide-induced apoptosis in NZB mice, restoring them to levels similar to those seen in BALB/c controls. Neurotropin, however, did not appear to have a significant influence in vitro which could be detected early. These data support the premise that neurotropin is most effective in vivo and also further substantiates the role of thymic microenvironmental abnormalities in the possible pathogenesis of murine lupus. The precise molecular mechanism by which neurotropin modulates the in vivo apoptosis of thymocytes is currently under study.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalInternational Journal of Immunotherapy
Volume15
Issue number2
StatePublished - 1999

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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