Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFα

Objectives: To evaluate the effect of anti-TNF alpha on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA). Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry. Results: At baseline the percentage of T cells positive for IFN gamma (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while ILIO (p=0.001) was increased. This cytokine profile, confirmed 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 patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFN gamma and IL2 in patients with SpA. Moreover, there was a transient decrease in ILIO and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. 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 blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine 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 alpha blockade.Objectives: To evaluate the effect of anti-TNF alpha on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA). Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry. Results: At baseline the percentage of T cells positive for IFN gamma (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while ILIO (p=0.001) was increased. This cytokine profile, confirmed 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 patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFN gamma and IL2 in patients with SpA. Moreover, there was a transient decrease in ILIO and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. 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 blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine 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 alpha blockade.A