Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis

Neuroimmunomodulation. 2019;26(3):129-138. doi: 10.1159/000500094. Epub 2019 May 27.

Abstract

Objective: We examined the effect of β-adrenoceptor (AR) blockade in the preclinical phase of experimental autoimmune encephalomyelitis (EAE), the most commonly used model of multiple sclerosis, on the development of primary CD4+ T-cell responses in draining lymph nodes (dLNs).

Methods: CD11b+ cell migration to dLNs, CD4+ T-cell activation/proliferation, and IL-17+ CD4+ (Th17) cell numbers in dLN and spinal cord (SC) were examined in male and female Dark Agouti rats using flow cytometry analysis.

Results: Irrespective of sex, in propranolol-treated (PT) rats, migration of CD11b+ antigen-presenting cells from the site of immunization to dLNs was impaired compared with saline-treated controls and consequently the frequency of all CD11b+ cells in dLNs and activated cells among them, too. This correlated with decreased expression of CCL19/21 transcripts in dLNs. Consistently, the frequency of activated/proliferating cells among dLN CD4+ T cells was reduced in PT rats. Additionally, propranolol reduced the number of Th17 cells in dLNs and SC. Consistently, male and female PT rats exhibited a decreased incidence of EAE and prolonged duration of the asymptomatic disease phase.

Conclusion: This study suggests that sympathetic dysregulation is involved in the outbreak of clinical EAE.

Keywords: Antigen-presenting cell migration; CCL19; CCL21; Experimental autoimmune encephalomyelitis; Th17 lymphocytes; β-Adrenoceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Movement / drug effects
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Male
  • Propranolol / pharmacology*
  • Rats
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / pathology

Substances

  • Adrenergic beta-Antagonists
  • Propranolol