Modification of neutrophil function by plasma of rheumatoid arthritis patients treated with infliximab L. Dain 1 , Y. Braun-Moscovici 1 , E. Baum 2 , A.M. Nahir 1 , E. Hoffer 2 1 B. Shine Department of Rheumatology and 2 Israel Poison Information Center, Rambam Medical Center, Haifa, Israel. Abstract Objective To examine whether the release of superoxide anions from neutrophils of healthy donors was affected when incubated with plasma from infliximab-treated rheumatoid arthritis (RA) patients. Methods Fifteen consecutive seropositive RA patients were treated with 3mg/kg infliximab on weeks 0, 2, 6, and 14. Disease activity was assessed by DAS28 score and by IL-6 level. Neutrophils from healthy donors were incubated with plasma drawn before each infliximab treatment. PMA-stimulated superoxide release was measured by the ferricytochrome C reduction method. Results 53% of the patients had a favorable clinical response. IL-6 levels showed a significant decline at week two, with a gradual increase thereafter. Treatment with infliximab did not change the superoxide production. However, when the group was divided retrospectively to responders (∆DAS28 > -1.2) and non-responders (∆DAS28 < -1.2), two different patterns were seen, although the pre-treatment levels were similar: Among the responders IL-6 remained low at its 2 weeks level till week 14, while in the non responders IL-6 increased 3 times (P < 0.03) from week 2 to 14. The responders showed mild, but continuous, reduction of superoxide release, while in the non-responders it increased significantly from week 2 on. Conclusions The reduction in IL-6 in RA sera following anti-TNFα therapy has little influence on the capacity of these sera to stimulate healthy neutrophils to produce superoxide, suggesting the existence of non-TNFα non-IL-6 dependent neu- trophil-stimulating mediators in RA sera. The increasing level of IL-6 among the non-responders after initial dramat- ic decline might represent an escape phenomenon, possibly caused by alternative mediator(s). Clinically, this IL-6 “escape” might be used as a tool for early identification of responders from non-responders. Key words Anti-tumor necrosis factor-α, neutrophils, rheumatoid arthritis, infliximab, superoxide anion production. Clinical and Experimental Rheumatology 2006; 24: 38-44.