Comparative in vitro investigations of the influence of mofebutazone, phenylbutazone and diclofenac on phagocytosis and respiratory burst of human peripheral blood leucocytes.
The phagocytosis and the release of oxidative products generated by the respiratory burst have been studied under the influence of the non-steroidal anti-inflammatories (NSAID) phenylbutazone (PB), mofebutazone (monophenylbutazone, MPB) and diclofenac (DF) using phagocytes of the peripheral blood from healthy human donors and patients with soft tissue rheumatism. The measurement of phagocytosis by flow cytometry (FC) was carried out in order to investigate the uptake of FITC-labelled bacteria (E. coli), separately by monocytes (MON) and polymorphonuclear leucocytes (PMN). In addition the luminol-dependent chemiluminescence (CL) was measured using opsonized Zymosan on leucocytes of the peripheral blood that were purified by lysis of erythrocytes. In FC, PMNs and MONs could be identified by gating in the whole blood in which erythrocytes had been lysed. The NSAID were added to the in vitro tests for 30 min in concentrations of 10(-3) mol/l, 10(-4) mol/l, 10(-5) mol/l, 10(-6) mol/l, and 10(-8) mol/l. Using the FC phagocytosis test it was found that PB and MPB decreased the percentage of phagocytosing PMNs as well as MONs while DF increased it slightly in contrast to the controls. However, the fluorescence intensity of the phagocytes, which indicates the amount of ingested bacteria, was found to be unchanged. PB effected a significant concentration-dependent inhibition of CL in all of the concentrations used, with the exception of 10(-8) mol/l. MPB resulted in a borderline inhibition at 10(-3) mol/l although the measurement of every individual proband showed a concentration dependency. DF inhibited the luminol-dependent CL significantly only at a concentration of 10(-3) mol/l.
Ludwig Boltzmann Institute of Rheumatology and Balneology, Vienna-Oberlaa, Austria.
J
J
Neumüller
M
M
Tohidast-Akrad
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D010653:Phenylbutazone / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D004008:Diclofenac; D015054:Zymosan; D010653:Phenylbutazone; C002374:mofebutazone