A transforming growth factor-β1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura

Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta 1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of tune Th3 cytokine TGF-beta 1 in patients with pltc > 150 x 10(9)/l (23.5 +/- 2.8 ng/ml), compared with patients with pltc < 50 x 10(9)/l (2.3 +/- 0.6 ng/ml; P < 0.0001), patients with pltc 50-150 x 10(9)/l (7.2 +/- 1.7 ng/ml; P < 0.0001) and healthy volunteers (9.8 +/- 1.3 ng/ml; P < 0.01). The serum levels of the Th1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc < 50 x 10(9)/l had significantly lower levels (0.6 +/- 0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P < 0.005) and healthy volunteers (1.4 +/- 0.1 pg/ml; P < 0.005). Furthermore, patients with pltc < 50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4+ CD25+ activated T cells [26.2 +/- 14.8% (P < 0.05) and 26.7 +/- 11.9% (P < 0.005), respectively] than healthy controls (16.5 +/- 4.0%). Also, the number of natural killer (NK) cells among patients with pltc > 150 x 10(9)/l were significantly elevated (26.6 +/- 16.0%; P < 0.05) compared with controls (17.4 +/- 7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta 1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta 1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.