Effect of anti-TNF-α therapy on neutrophil activity in patients with rheumatoid arthritis
2014
Neutrophils are known to contribute to rheumatoid arthritis (RA) pathogenesis via protease release and toxic reactive oxygen species (ROS) production, as well as by generation of a number of cytokines and chemokines. On the other hand, antagonists of pro-inflammatory cytokine tumor necrosis factor - alpha (TNF-?), a new class of drugs already used to treat RA, have shown beneficial therapeutic results. Although several studies reported participation of neutrophils in anti-inflammatory action of anti-TNF-? agents, precise explanation of their role is still studied and discussed. We evaluated the effect of anti-TNF-? therapy on the activity of peripheral blood neutrophils and on relative levels of selected cytokines and chemokines in plasma obtained from patients suffering from RA. Blood samples were obtained from control subjects (n=13) and from patients (n=3) with active RA, as defined by the Disease Activity Score (DAS 28 >5.1), before and 4 months after onset of anti-TNF-? therapy. As the parameter of activity, generation of ROS was evaluated in whole blood by luminol amplified chemiluminescence. The relative levels of selected cytokines and chemokines in plasma were determined by Proteome ProfilerTM, Human Cytokine Array Panel A. In comparison with control subjects, RA patients exibited increase of i) neutrophils number and ROS production in peripheral blood unstimulated and stimulated with receptor dependent stimuli (N-formyl-methionyl-leucyl-phenyl-alanine, opsonized zymosan) and receptor independent stimuli (phorbol 12-myristate-13-acetate, Ca ionophore A23187), and ii) of relative levels of selected cytokines and chemokines (G-CSF, CXCL1, CCL1, IL-1ra, IL-13, IL-16, IL-17E) in plasma. Despite the restricted number of patients with active RA the results showed both that antagonists of TNF-? decreased spontaneous and stimulated neutrophils activity (manifesteted by decrease of neutrophil numer and ROS production), as compared to values before therapy, and they were more effective after receptor dependent stimulation of neutrophils. The levels of selected cytokines and chemokines, important for driving inflammatory responses, were also attenuated by antagonists of TNF-?. .
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