PMID- 10319886
OWN - NLM
STAT- MEDLINE
DCOM- 19990525
LR  - 20191024
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 45
IP  - 5
DP  - 1999 May
TI  - Dysregulation of adenosine A1 receptor-mediated cytokine expression in peripheral 
      blood mononuclear cells from multiple sclerosis patients.
PG  - 633-9
AB  - Cytokines, including tumor necrosis factor-alpha (TNF alpha) 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 TNF alpha levels, A1 receptor messenger RNA (mRNA) and protein 
      amounts, and the effects of activation of A1 receptors on TNF alpha and IL-6 
      production by PBMCs. Plasma levels of TNF alpha were significantly higher and 
      adenosine levels were significantly lower in MS patients compared with control 
      subjects. Levels of TNF alpha 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 microM) significantly inhibited 
      mitogen-stimulated production of TNF alpha but not IL-6 in control subjects and 
      significantly inhibited production of IL-6 but not TNF alpha in MS patients. The 
      effects of R-PIA were selectively blocked by the A1 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 TNF alpha 
      and IL-6 levels and may contribute to the pathogenesis of MS.
FAU - Mayne, M
AU  - Mayne M
AD  - Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, 
      Canada.
FAU - Shepel, P N
AU  - Shepel PN
FAU - Jiang, Y
AU  - Jiang Y
FAU - Geiger, J D
AU  - Geiger JD
FAU - Power, C
AU  - Power C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/blood
MH  - Adult
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Monocytes/*metabolism
MH  - Multiple Sclerosis/*blood
MH  - Receptors, Purinergic P1/blood/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1002/1531-8249(199905)45:5<633::aid-ana12>3.0.co;2-x [doi]
PST - ppublish
SO  - Ann Neurol. 1999 May;45(5):633-9. doi: 
      10.1002/1531-8249(199905)45:5<633::aid-ana12>3.0.co;2-x.