Purine modulation of cytokine release during diuretic therapy of rheumatoid arthritis.
Since free radicals are implicated in rheumatoid arthritis (RA) and since uric acid is a free radical scavenger, we examined the effects of treating RA patients with with the diuretic bumetanide to try to improve their arthritic control. Seventy patients, aged 18-75 years, were randomised to receive bumetanide 4 mg/day or placebo. Uric acid levels increased, but not that of other purines, in the blood of drug-treated patients compared with placebo-treated controls. There were no significant changes in clinical measurements of disease activity or in ESR or CRP levels. There were no over all differences in the blood levels of the cytokines, nor in the basal or stimulated production of cytokines from the blood cultures. The adenosine receptor agonist 5'N-ethylcarboxamido-adenosine (NECA) used to modify cytokine release in cultures of whole blood taken from the patients, depressed the release of tumour necrosis factor-alpha (TNFalpha), but failed to depress the release of interleukin-1b (IL-1b) or interleukin-6 (IL-6), a difference from earlier studies of healthy control subjects and, thus, a difference which may contribute to the disease activity.
Forrest
C M
CM
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
Harman
G
G
McMillan
R B
RB
Rana
C
C
Shaw
S
S
Stone
T W
TW
Stoy
N
N
Darlington
L G
LG
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D002034:Bumetanide / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008875:Middle Aged; D010919:Placebos; D011687:Purines / Q000737:chemistry / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D016207:Cytokines; D016166:Free Radical Scavengers; D005609:Free Radicals; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010919:Placebos; D011687:Purines; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha; D002034:Bumetanide; D014527:Uric Acid; D019830:Adenosine-5'-(N-ethylcarboxamide)