Nitric oxide synthase inhibitor influences prostaglandin and interleukin-1 production in experimental arthritic joints.
OBJECTIVE
To assess involvement of nitric oxide (NO) in the increase in eicosanoid and interleukin- 1 (IL-1) levels in the synovial fluid during antigen-induced arthritis (AIA) in rabbits treated with a competitive inhibitor of NO synthesis.


METHODS
Thirteen New Zealand White rabbits were sensitized with 5 mg of methylated bovine serum albumin (mBSA). Arthritis was induced in the knee joint by injecting 0.5 ml of a sterile solution of mBSA (2 mg/ml) into the intra-articular cavity.


METHODS
Prior to the induction of arthritis, the animals received N-Omega-Nitro-L-Arginine Methyl Ester (LNAME) or N-Omega-Nitro-D-Arginine Methyl Ester (DNAME) for 2 weeks, both at a dose of 20 mg/kg/day mixed with drinking water.


METHODS
Leukocyte efflux (total and differential white cell count), vascular permeability (Evans's blue method), synovial PMN cell infiltrate, and total nitrite (NO2.)/nitrate (NO3.) (HPLC), PGE2, TxB2, LTB4 (radioimmunoassay), and IL-1 beta (ELISA) levels were quantified in the synovial fluid.


RESULTS
LNAME but not DNAME significantly suppressed leukocyte efflux and protein leakage into the articular cavity as well as synovial PMN cell infiltrate. Total NO2./NO3., PGE2 and IL-1 beta levels were significantly reduced in the synovial fluid of LNAME treated animals. TxB2 and LTB4 were not affected by LNAME treatment.


CONCLUSIONS
These data clearly show NO involvement in the IL-1-induced PGE2 production in the synovial fluid of antigen-induced arthritis in rabbits.
de Mello
S B
SB
Rheumatology Division, School of Medicine, University of São Paulo, Brazil.
Novaes
G S
GS
Laurindo
I M
IM
Muscará
M N
MN
Maciel
F M
FM
Cossermelli
W
W
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000009:adverse effects / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000737:chemistry; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D011817:Rabbits; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000473:pathology
D015777:Eicosanoids; D007375:Interleukin-1; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015232:Dinoprostone