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

Objectives—To evaluate the eVect of antiTNFá 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)ã 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 IFNã (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 IFNã 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. TNFá blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the eVect of antiTNFá on the immune changes in SpA, and provide insights into the mechanisms involved in TNFá blockade. (Ann Rheum Dis 2001;60:750–755) Analogous with the findings in mice, human CD4+ T cells are classically divided into two subsets with regard to their cytokine secretion: Th1 cells which mainly secrete IFNã and IL2, and Th2 cells which are characterised by the production of IL4, IL5, and IL10. With regard to the distinct functional properties of Th1 and Th2 cells, Th1 polarisation has been implicated in the pathogenesis of autoimmune disorders including diVerent forms of experimental and human arthritis, particularly rheumatoid arthritis (RA). 4 However, Th1 polarisation has not been confirmed in spondyloarthropathy (SpA), a group of related chronic autoimmune diseases of the joint with common clinical, radiological, and genetic characteristics, and there is increasing evidence that SpA is functionally characterised by a Th2 cytokine profile. A recent open label pilot study evaluating the eVect of anti-TNFá in SpA indicated a dramatic clinical improvement in both axial and peripheral joint inflammation. Since TNFá blockade influences T cell cytokines both in vitro and in vivo, the eVect of TNFá blockade in SpA could partially be mediated by alterations in Th1 and Th2 cytokine production. The aim of the present study was therefore to investigate the eVect of anti-TNFá on Th1 and Th2 cytokine production in patients with SpA, to confirm the impact on immune changes in SpA, and to provide insights into the mechanisms that could be involved in TNFá blockade in SpA. In addition to the cytokines IFNã, IL2, IL4, and IL10, the study pays special attention to natural killer (NK) T cells. This T cell subset, which shares characteristics of both T cells and NK cells, is a potent cytokine producing cell population with an important regulatory function on Th1/Th2 immune responses. 18 Subjects and methods