Neutrophil functional and arachidonic acid metabolic correlates and clinical disease activity in pirazolac-treated rheumatoid arthritis patients.
Neutrophils from 20 medication-free rheumatoid arthritis patients were chemotactically hyporesponsive to 2 x 10(-8) M formyl-methionyl-leucyl-phenylalanine (f-MLP) as compared to 20 normal controls. They were relatively high producers of 5-hydroxyeicosatetraenoic acid (5-HETE) and low producers of leukotriene C4 (LTC4). Neutrophils from 10 patients treated with pirazolac (4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-pyrazole acetic acid) showed increased chemotactic responsiveness concomitantly with normalization of 5-HETE and LTC4 production and a decrease in the clinical parameters of disease activity. Clinically attainable (30-60 micrograms/ml) in-vitro doses of pirazolac further depressed the chemotactic responsiveness of normal neutrophils treated with 10(-5)M f-MLP. Effects on endothelial gating of migrating neutrophil populations may explain this apparent contradiction between in-vivo and in-vitro actions of pirazolac on neutrophil chemotaxis.
Turner
R A
RA
Department of Medicine, Bowan Gray School of Medicine, Wake Forest University, Winston-Salem, NC.
Johnson
J A
JA
Turner
S R
SR
McGee
M
M
Kashanian
F
F
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000627:therapeutic use*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011720:Pyrazoles / Q000097:blood / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D011720:Pyrazoles; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C046317:pirazolac