Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis

Chris L. Ayers, Jason P. Mendoza, Sushmita Sinha, Khrishen Cunnusamy, Benjamin Greenberg, Elliot Frohman, Nitin J. Karandikar

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Daily administration of FDA-approved glatiramer acetate (GA) has beneficial effects on clinical course of relapsing remitting multiple sclerosis (RRMS). Although mechanisms of GA-action have been widely investigated and partially understood, immediate immune dynamics following GA-therapy are unknown. In the present study, we characterized the immediate effects of GA on phenotype, quantity and function of immune cells in MS patients. Prominent changes in immune cells were detected within 4-12. h post-first GA-injection. T-cell modulation included significantly decreased CD4/CD8 ratio, perturbed homeostasis of predominantly CD8. + T-cells, significant enhancement in CD8. + T-cell mediated suppression and inhibitory potential of induced CD4-suppressors. Changes in APC were restricted to monocytes and included reduced stimulatory capacity in MLR and significantly increased IL-10 and TNF-α production. Our study provides the first evidence that GA treatment induces rapid immunologic changes within hours of first dose. Interestingly, these responses are not only restricted to innate immune cells but also include complex modulation of T-cell functionality.

Original languageEnglish (US)
Pages (from-to)105-119
Number of pages15
JournalClinical Immunology
Volume147
Issue number2
DOIs
StatePublished - May 1 2013

Keywords

  • Glatiramer acetate
  • Immunomodulation
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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