Differential function of nitric oxide in murine antigen-induced arthritis.
BACKGROUND
The aim of our study was to investigate the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in different stages of murine antigen-induced arthritis (AiA).


METHODS
Clinical, histological and microcirculatory parameters (measured by intravital fluorescence microscopy) were assessed in the knee joint during acute and chronic AiA after inhibition of iNOS with L-N(6)-(1-iminoethyl)lysine (L-NIL). Plasma concentrations of and were evaluated by the Griess reaction and the expression of iNOS, P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by immunohistochemistry.


RESULTS
In both stages of the disease, plasma concentrations of and were increased and iNOS was expressed. In the acute phase, swelling, leucocyte adhesion, leucocyte infiltration and expression of adhesion molecules were increased in arthritic animals treated with L-NIL in comparison with untreated arthritic animals. In the chronic phase, no change in the disease parameters could be detected after L-NIL treatment.


CONCLUSIONS
Increased NO production induced by iNOS during the acute phase of AiA can be regarded as a protective response in the prevention of further leucocytic infiltration and joint destruction, whereas it seems to play a subordinate role in chronic AiA.
Veihelmann
A
A
Department of Orthopaedics, Ludwig Maximilians University of Munich, Munich, Germany.
Hofbauer
A
A
Krombach
F
F
Dorger
M
M
Maier
M
M
Refior
H-J
HJ
Messmer
K
K
D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007091:Image Processing, Computer-Assisted; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D019087:Selectins / Q000378:metabolism; D013264:Stifle / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects / Q000473:pathology
D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D009566:Nitrates; D009573:Nitrites; D019087:Selectins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008239:Lysine