Effect of piroxicam therapy on granulocyte function and granulocyte elastase concentration in peripheral blood and synovial fluid of rheumatoid arthritis patients.
The effect of piroxicam therapy (20 mg/day for 15 days) on various polymorphonuclear granulocyte (PMN) responses and on PMN elastase concentration was investigated in nine patients with active rheumatoid arthritis. Peripheral blood and synovial fluid samples were collected before starting therapy and 12 h after the last dose of the drug. All patients were evaluable for peripheral blood analysis and six for synovial fluid analysis. Piroxicam therapy had no effect on PMN random migration and phagocytosis, while it significantly reduced both FMLP-induced aggregation and FMLP-induced chemotaxis. This seems mainly due to an effect on FMLP binding, as no differences were observed after therapy in PMA- and PHA-induced aggregation as well as in serum-induced chemotaxis. In contrast, a marked impairment of NBT test and PMA- and FMLP-induced superoxide anion (O2-) production was found after piroxicam therapy. This effect was as evident in peripheral blood as in synovial fluid PMN. Also, a significant reduction in synovial fluid PMN number and synovial fluid PMN elastase concentration (elastase-alpha 1-proteinase complex) was found after treatment. It is concluded that piroxicam may act at different sites on various PMN responses. Its effect on O2- generation and PMN elastase concentration in synovial fluid may have an important role in reducing destruction of arthritic joint tissue.
Montecucco
C
C
Dipartimento di Medicina Interna e Terapia Medica, Università di Pavia-IRCCS Policlinico S. Matteo, Italy.
Mazzone
A
A
Pasotti
D
D
Caporali
R
R
Longhi
M
M
Casilli
D
D
Ricevuti
G
G
Fratino
P
P
Ruffilli
M P
MP
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D001798:Blood Proteins / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010196:Pancreatic Elastase / Q000097:blood* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D010894:Piroxicam / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D010894:Piroxicam; D010196:Pancreatic Elastase