Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNF alpha

Objectives-To evaluate the effect of anti-TNF alpha on the Th1 and Th2 cyto kines in patients with spondyloarthropathy (SpA). Methods-Peripheral blood mononuclear cells (PBMC) were obtained from 20 pat ients with active SpA treated with infliximab (5 mg/kg). For comparison, PB MC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intrac ellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma w ere determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cell s by flow cytometry. Results-At baseline the percentage of T cells positive for IFN gamma (p=0.0 20) and IL2 (p=0.046) was decreased in patients with SpA compared with heal thy controls, while ILIO (p=0.001) was increased. This cytokine profile, co nfirmed by the mean fluorescence intensities (MFI), was more pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK T cells , characterised by high IL4 and ILIO numbers, were also increased in patien ts with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFN gamma and IL2 in patients with SpA. Moreover, th ere was a transient decrease in ILIO and NK T cells in patients with high b aseline values, resulting in values comparable with those of healthy contro ls. This switch in cytokine profile was seen in both the CD3+/ CD8- and CD3 +/CD8+ subsets. Conclusions-Before treatment patients with SpA had an impaired Th1 cytokine profile compared with healthy controls and patients with RA. TNF alpha blo ckade induced restoration of the Th1 cytokines, resulting in a normal cytok ine balance. These data confirm the effect of anti-TNF alpha on the immune changes in SpA, and provide insights into the mechanisms involved in TNF al pha blockade.