Selectins and IL-6 during the Clinical Course of Idiopathic Thrombocytopenic Purpura

Abstract

‘Stress thrombocytes’, i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = –0.32, p = 0.019) and IL-6 (r = –0.41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented ‘residual platelet’ functions in ITP.

Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia

“…Circulating levels of IL-6 have been reported to be elevated in ITP and to increase with increasing disease activity, which might reflect IL-6 mediating a compensatory megakaryocytopoiesis. 38 B-cell counts were still significantly reduced 12 months after initi- Given the role of CD5 + B cells in maintenance of tolerance, 33 the high frequency of these cells, which has also been observed after RTX therapy in rheumatoid arthritis, 39 is compatible with amelioration of disease. Indeed, decreased CD5 + B-cell counts were observed in active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis 29,40 but normalized after RTX treatment.…”

Thrombocytopenia in HIV Disease: Clinical Relevance, Physiopathology and Management

“…Several of these cytokines, alone or in combination, have undergone extensive preclinical and clinical testing [59,[142][143][144]. Given that both the immune and hematopoietic systems originate from a common stem cell and are initially regulated by the same family of cytokines, which include IL-3, IL-11, IL6, and thrombopoietin (TPO), establishing the interaction of these two systems is of critical importance, particularly in the setting of HIV [145].…”

Effect of P-Selectin on Phosphatidylserine Exposure and Surface-Dependent Thrombin Generation on Monocytes

“…Such an effect may be advantageous in settings such as autoimmune thrombocytopenia, in which a bleeding tendency coexists with elevated levels of plasma sP-selectin. 31 Treatment with the anti-PSGL-1 blocking monoclonal antibody, KPL-1, prevented nearly all the exposure of phosphatidylserine induced by sP-selectin, indicating that PSGL-1 is the receptor on the monocyte surface mediating the effects elicited by sP-selectin. There is internal consistency between these findings and those of several studies.…”