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.
