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

D Baeten, N Van Damme, F Van den Bosch… - Annals of the …, 2001 - ard.bmj.com
D Baeten, N Van Damme, F Van den Bosch, E Kruithof, M De Vos, H Mielants, EM Veys…
Annals of the Rheumatic Diseases, 2001ard.bmj.com
OBJECTIVES To evaluate the effect of anti-TNFα 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) γ were determined in CD3+ T cells and in …
OBJECTIVES
To evaluate the effect of anti-TNFα 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)γ 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 IFNγ (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while IL10 (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 IL10 numbers, were also increased in patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFNγ and IL2 in patients with SpA. Moreover, there was a transient decrease in IL10 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. TNFα blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the effect of anti-TNFα on the immune changes in SpA, and provide insights into the mechanisms involved in TNFα blockade.
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