Inhibition of 5-lipoxygenase product formation and polymorphonuclear cell degranulation by tenidap sodium in patients with rheumatoid arthritis.
We studied the effect of tenidap sodium, a new antiinflammatory/antirheumatic drug (120 mg/day for 7 days), on eicosanoid production and neutrophil degranulation in patients with rheumatoid arthritis. Endogenous prostaglandin E2 levels and ex vivo production of leukotriene B4 (LTB4) were measured in synovial fluid samples obtained at baseline and 1 week later. We measured peripheral blood polymorphonuclear cell (PMN) degranulation following surface-bound IgG stimulation, a possible 5-lipoxygenase product-mediated event, by determining lactoferrin and elastase release into the culture fluid. We found decreased levels of endogenous prostaglandin E2 as measured by radioimmunoassay, and decreased ex vivo production of LTB4 by PMN as measured by high performance liquid chromatography, in synovial fluid samples from patients who took tenidap. Release of the granule proteins lactoferrin and elastase was decreased in PMN obtained from patients receiving tenidap, as well as in the PMN incubated in vitro with tenidap. Improvement in clinical measures paralleled the biochemical changes. The unique 5-lipoxygenase inhibitory property of tenidap, as measured by LTB4 production and degranulation, suggests that it may have clinical activity which differentiates it from nonsteroidal antiinflammatory drugs.
Blackburn
W D
WD
Department of Medicine, Birmingham Veterans Administration Medical Center, AL 35233.
Heck
L W
LW
Loose
L D
LD
Eskra
J D
JD
Carty
T J
TJ
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007781:Lactoferrin / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D000078183:Oxindoles; D010196:Pancreatic Elastase / Q000378:metabolism; D011863:Radioimmunoassay; D013582:Synovial Fluid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D000078183:Oxindoles; D007975:Leukotriene B4; C062866:tenidap; D007781:Lactoferrin; D010196:Pancreatic Elastase; D015232:Dinoprostone