Regulation of nitric oxide production in osteoarthritic and rheumatoid cartilage. Role of endogenous IL-1 inhibitors.
OBJECTIVE
To investigate the endogenous regulation of interleukin-1 (IL-1) cytokine network in osteoarthritic (OA) and rheumatoid (RA) cartilage in relation to nitric oxide (NO) production.


METHODS
Cartilage specimen obtained from OA and RA patients undergoing knee replacement surgery were studied for iNOS expression, NO and IL-1 antagonist production in tissue culture.


RESULTS
OA cartilage responded to IL-1beta-stimulation with higher NO production than RA cartilage, whereas there was no difference in NO synthesis between OA and RA samples when stimulated by TNFalpha or LPS. Interleukin-1 receptor antagonist (IL-1Ra) production was higher in RA cartilage than in OA cartilage, and its production was increased by NO synthase inhibitor 1400W.


CONCLUSIONS
IL-1beta is a potent stimulator of NO production by the iNOS pathway in RA and more pronouncedly in OA cartilage. This process is regulated by cartilage derived IL-1 antagonists, and is implicated in cartilage destruction and synovial inflammation in OA and RA joints.
Vuolteenaho
Katriina
K
The Immunopharmacological Research Group, Medical School, University of Tampere, and Tampere University Hospital, Finland.
Moilanen
Taemu
T
Hämäläinen
Mari
M
Moilanen
Eeve
E
D000368:Aged; D000369:Aged, 80 and over; D000578:Amidines / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001596:Benzylamines / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000578:Amidines; D019138:Antibodies, Blocking; D001596:Benzylamines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II