OXIDATIVE BURST OF NEUTROPHILS IN PATIENTS WITH RHEUMATOID-ARTHRITIS - INFLUENCE OF VARIOUS CYTOKINES AND MEDICATION

Objective. Toxic oxygen products are believed to be implicated in tiss ue damage in some complex-mediated diseases such as rheumatoid arthrit is. In the present study we compared the superoxide (O-2(-)) productio n of polymorphonuclear leukocytes (PMNs) in 21 patients with rheumatoi d arthritis (RA) with that of 9 healthy controls, examining the effect of different stimulants and cytokines on the oxidative burst (OB). Si nce many drugs used in the treatment of RA may alter O-2 metabolism, t he effects of antirheumatic medication were also studied. Methods. Gen eration of superoxide anions was analysed by a flow cytometric method, using the fluorochrome dihydro-rhodamine. As stimulants for OB, we us ed N-formyl-methionyl-leucyl-phenylalanine (fMLP), which acts via a me mbrane receptor, and phorbol-myristate acetate (PMA), which acts in a membrane receptor-independent manner As preactivating substances, TNF- alpha, G-CSF and GM-CSF were applied. Results. In RA patients under tr eatment with antirheumatic medication, fMLP-induced OB (+/- cytokines) was significantly reduced, while O-2(-) production after stimulation with PMA was similar compared to controls. GM-CSF showed the highest l evel of preactivation in controls, whereas in RA patients TNF-alpha pr oved to be most potent. In both controls and RA patients, a combinatio n of GM-CSF or G-CSF with TNF-alpha further enhanced OB. No correlatio n between OB and clinical data or treatment could be established in RA patients. Conclusions. There is a reduced cytokine priming capacity f or OB in RA patients under antirheumatic medication in spite of the pr esence of an intact enzyme system of OB. Antirheumatic medication comb ining multiple drugs capable of decreasing OB might effectively modula te oxidative metabolism.