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 tissue damage in some complex-mediated diseases such as rheumatoid arthritis. In the present study we compared the superoxide (O2) production of polymorphonuclear leukocytes (PMNs) in 21 patients with rheumatoid arthritis (RA) with that of 9 healthy controls, examining the effect of different stimulants and cytokines on the oxidative burst (OB). Since many drugs used in the treatment of RA may alter O2 metabolism, the effects of antirheumatic medication were also studied.

METHODS

Generation of superoxide anions was analysed by a flow cytometric method, using the fluorochrome dihydro-rhodamine. As stimulants for OB, we used N-formyl-methionyl-leucyl-phenylalanine (fMLP), which acts via a membrane 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 treatment with antirheumatic medication, fMLP-induced OB (+/- cytokines) was significantly reduced, while O2 production after stimulation with PMA was similar compared to controls. GM-CSF showed the highest level of preactivation in controls, whereas in RA patients TNF-alpha proved to be most potent. In both controls and RA patients, a combination of GM-CSF or G-CSF with TNF-alpha further enhanced OB. No correlation between OB and clinical data or treatment could be established in RA patients.

CONCLUSIONS

There is a reduced cytokine priming capacity for OB in RA patients under antirheumatic medication in spite of the presence of an intact enzyme system of OB. Antirheumatic medication combining multiple drugs capable of decreasing OB might effectively modulate oxidative metabolism.