Dysregulation of adenosine A1 receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients

M. Mayne, P. N. Shepel, Y. Jiang, J. D. Geiger, C. Power

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Cytokines, including tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), have been implicated in the pathogenesis of multiple sclerosis (MS). The production and release of these cytokines are regulated in part by specific purinergic (adenosine) cell surface receptors. To determine the extent to which the adenosine A1 receptor influenced cytokine expression in peripheral blood mononuclear cells (PBMCs) from MS and control patients, we measured plasma adenosine and TNFα levels, A1 receptor messenger RNA (mRNA) and protein amounts, and the effects of activation of A1 receptors on TNFα and IL-6 production by PBMCs. Plasma levels of TNFα were significantly higher and adenosine levels were significantly lower in MS patients compared with control subjects. Levels of TNFα and IL-6 in mitogen-stimulated PBMC culture supernatants from MS patients or control patients were similar. Conversely, treatment of PBMCs with the adenosine A1 receptor agonist R- phenylisopropyladenosine (R-PIA) (1 μM) significantly inhibited mitogen- stimulated production of TNFα but not IL-6 in control subjects and significantly inhibited production of IL-6 but not TNFα in MS patients. The effects of R-PIA were selectively blocked by the at receptor antagonist 8- cyclopentyl-1,3-dipropylxanthine (DPCPX). A1 receptor protein levels were decreased significantly in PBMCs from MS patients. Taken together, these results suggest that decreased levels of adenosine and its A1 receptor modulate TNFα and IL-6 levels and may contribute to the pathogenesis of MS.

Original languageEnglish (US)
Pages (from-to)633-639
Number of pages7
JournalAnnals of Neurology
Volume45
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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