Thrombopoietic cytokines in relation to platelet recovery after bone marrow transplantation

In order to evaluate the importance of different thrombopoietic stimulatory cytokines in accelerating platelet recovery after bone marrow transplantation (BMT), we assayed serial plasma concentrations of three cytokines, thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 through the course of platelet nadir and recovery after BMT. Both mean TPO and IL-6 levels showed a marked rise and later fall preceding or coincident with the platelet nadir and recovery, suggesting their potential role as circulating regulators or stimulators of thrombopoiesis. In contrast, IL-11 levels remained remarkably constant through the whole course suggesting that this cytokine, though capable of stimulating thrombopoiesis, does not serve as a circulating regulator of platelet production. Additionally, we assayed the levels of these three cytokines following initial platelet transfusion to assess the capacity of transfused platelets to adsorb these thrombopoietic cytokines from the plasma and reduce their circulating levels, thus potentially modifying their availability for stimulating megakaryocyte proliferation. No consistent falls in TPO, IL-6 or IL-11 levels were observed following the initial two platelet transfusions. These data support the importance of circulating TPO and IL-6 as hormones capable of stimulating platelet production. Their physiologic relevance as in vivo regulators of thrombopoiesis and clinical utility for therapy of thrombocytopenia need further investigation.     

Thrombopoietic cytokines and reversal of thrombocytopenia after liver transplantation

OBJECTIVES: Thrombopoietin (TPO), the key regulator of platelet production, is mainly produced by the liver and reduced expression of TPO could cause thrombocytopenia in liver cirrhosis. Reversal of thrombocytopenia by orthotopic liver transplantation seems to be mediated through an increase in TPO plasma levels after transplantation, but other cytokines with thrombopoietic activity could augment the actions of TPO on post transplant platelet recovery. DESIGN: Measurement of thrombopoietic cytokines before and for 14 days post liver transplantation in a cohort of thrombocytopenic liver transplant patients. METHODS: TPO, interleukin-3 (IL-3), IL-6, and IL-11 plasma levels as well as peripheral platelet count were analysed in thrombocytopenic patients with liver disease undergoing orthotopic liver transplantation (17 patients) and followed for 14 days after the intervention. RESULTS: Before liver transplantation, TPO plasma levels were undetectable and IL-3, IL-6, and IL-11 levels were normal. Sixteen out of 17 patients showed a significant rise of TPO levels within 2 days after transplantation, with a peak between days 4 and 6, while IL-3 and IL-6 levels did not show a significant rise. IL-11 levels remained normal. Platelet counts were significantly higher than pretransplantation levels by day 14 post transplantation. CONCLUSION: Restitution of normal TPO production by liver replacement seems to be of key importance for reversal of thrombocytopenia in liver disease. The early acting thrombopoietic factor IL-3 and the late acting factors IL-6 and IL-11 do not play a major role for recovery of peripheral platelet count after orthotopic liver transplantation.     

Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea

Background

Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA.

Methods

Of 60 patients, 10 patients had mild OSA (AHI 5–14), 10 moderate (AHI 15–29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured.

Results

Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention.

Conclusions

Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.

     

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents

Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers.

Methods: The first follow-up data of 51 IBD patients (17 Crohn’s disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months.

Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients.

Conclusion: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31–41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.     

Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro

Thrombopoietin (Tpo), the ligand for the c-mpl receptor, is a major regulator of platelet production in vivo. Treatment of mice with purified recombinant Tpo increases platelet count fourfold and expands colony-forming unit-megakaryocyte (CFU-Meg) numbers. Other cytokines including interleukin-3 (IL-3), IL-6, IL-11, erythropoietin (Epo), and stem cell factor (SCF) can stimulate megakaryopoiesis. Therefore, we examined the effects of recombinant murine Tpo in combination with these cytokines on megakaryopoiesis in vitro. Murine marrow cells were cultured in agar in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% horse serum and beta-mercaptoethanol in the presence of recombinant growth factors, and CFU-Meg colonies were counted on day 5. Megakaryocyte ploidy was analyzed using murine marrow cells cultured for 5 days in IMDM supplemented with 1% nutridoma-SP and recombinant growth factors. Megakaryocytes were identified by labeling with the 4A5 antibody and ploidy was analyzed by flow cytometry. Tpo supported the growth of CFU-Meg in a dose-dependent manner. Although the addition of SCF (50 ng/mL), Epo (2 U/mL), or IL-11 (50 ng/mL) alone exerted only a modest effect on CFU-Meg growth, the combination of SCF plus Tpo, Epo plus Tpo, or IL-11 plus Tpo resulted in a synergistic enhancement of the number of CFU-Meg colonies. IL-3 alone supported CFU- Meg colony growth, and the effects of IL-3 plus Tpo or IL-6 plus Tpo on colony growth appeared to be approximately additive. Fifty percent of megakaryocytes generated in cultures containing IL-3 or Epo displayed < or = 16 N ploidy. In contrast, cultures containing Tpo uniquely generated large numbers (30% to 35% of the total) of megakaryocytes with > or = 64N ploidy. These results show that Tpo stimulates both proliferation of committed megakaryocytic progenitor cells and maturation of megakaryocytes, and that two multipotent cytokines, SCF and IL-11, as well as a late-acting erythroid cytokine, Epo, can synergize with Tpo to stimulate proliferation of CFU-Meg.     

Clinical significance of serum TNFα and -308 G/A promoter polymorphism and serum Il-6 and -174 G/C promoter polymorphism in systemic lupus erythematosus patients

IntroductionSystemic lupus erythematosus (SLE) is a disorder of immune regulation where cytokine imbalance and genetic factors are implicated in its pathogenesis.Aim of the workTo evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNFα) and its -308 G/A promoter polymorphism as well as the IL-6 and -174 promoter polymorphism in SLE patients and find any association to the clinical and laboratory features as well as to the disease activity and severity.Patients and methodsWe studied 37 female SLE patients and age and gender matched healthy control. Demographic, clinical and serological data were evaluated and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaboration Clinics/ACR Damage Index (SLICC) were assessed. Serum TNF-α and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and DNA genotyped for TNF-α promoter (-308 G/A) and IL-6 promoter (-174 G/C) by polymerase-chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis.ResultsSerum TNF-α and IL-6 levels were significantly higher in the SLE patients compared to control. Regarding IL-6, there was a statistically significant difference between the levels in the three groups according to the promoter polymorphisms. Patients with constitutional symptoms showed higher level of IL-6 while the TNF-α level was significantly lower in those with pulmonary manifestations. There was a tendency to a higher TNF-α and IL-6 level in those with neuropsychiatric manifestations.ConclusionSerum TNF-α, -308 G/A promoter polymorphism, IL-6 and -174 G/C were higher in SLE patients than in healthy controls. To confirm our results we propose that larger scale, multicenter studies with longer evaluation periods are needed.     

Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia

This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 10?/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P = .001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r2 = -0.578, P = .015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect.     

Stage classification of IgG4-related dacryoadenitis and sialadenitis by the serum cytokine environment

Abstract

Objectives: Patients with immunoglobulin-G4 related disease (IgG4-RD) diagnosed according to the comprehensive diagnostic criteria (CDC) show varied therapeutic responses and prognoses. We assumed that there are clinical stages in IgG4-RD and have verified it using serum cytokine levels in the groups classified by lesion distribution.

Methods: Definite IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) cases were divided according to the CDC for IgG4-RD into 11 cases with focal type and 30 cases with systemic type. The levels of serum interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-15, IL-21, interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and monocyte chemotactic protein (MCP)-1 were measured in healthy controls, allergic patients, probable IgG4-RD cases, and focal and systemic type cases. The cytokine environment was analyzed in each group. The 52 definite IgG4-RD cases were next classified into four groups with cluster analysis in terms of therapeutic responses and prognosis. The relationships between each cytokine level and therapeutic responses were also analyzed.

Results: Both serum IL-5 and IFN-α concentrations were very low in healthy controls, but they increased in the allergic cases, probable cases, and focal and systemic type cases. The level of serum IL-5 was significantly higher in definite cases than in healthy controls. The serum IL-5 level was also significantly increased in the groups with a poor prognosis than in the good prognosis group.

Conclusion: These results suggest that there are clinical stages in IgG4-RD, and serum IL-5 play roles in the pathogenesis of IgG4-RD.     

Relationship of mean platelet volume to platelet count in morphologic evaluation of thrombopoiesis

A graph of the relationship between mean platelet volume (MPV) and platelet count (TPK) was constructed out of 158 haematologically normal individuals, 19 patients with thrombocytopenia and 63 patients with thrombocytosis. Patients with thrombocytopenia and thrombocytosis whose bone marrows were found to show adequate or increased, morphologically normal, thrombopoiesis were included in the graph. The graph was found to exhibit the previously known inverse relationship between TPK and MPV extended into thrombocytopenic values and is thought to represent an intact marrow function capable of meeting the increased demands of thrombopoiesis. On the other hand, 15 patients whose bone marrows were showing evidence of hypoplastic thrombopoiesis fell outside the region representing intact marrow function. The position of an individual's values of MPV vs TPK in a coordinate system with these variables on the axes correlates well with the morphologic evaluation of thrombopoietic function and seems to be clinically useful.     

Tumor necrosis factor-alpha antagonist therapy-induced psoriasis in Turkey: analysis of 514 patients

Abstract

Objectives New adverse events are being reported with the increased use of anti-tumor necrosis factor (TNF) α therapy. We studied cases of anti-TNFα-induced psoriasis observed in our pool of 514 patients receiving anti-TNFα treatment in Turkey.

Methods Three rheumatoid arthritis patients and 3 ankylosing spondylitis patients with anti-TNFα-induced psoriasis were included in the study. All patients were examined by a dermatologist, and 3 patients underwent skin biopsy.

Results None of the 6 patients had preexisting psoriasis or a familial history of psoriasis. The earliest and latest occurrences of psoriatic lesions were at the 6th week and 44th month of anti-TNFα therapy, respectively. Psoriasis was severe and refractory in two patients (requiring systemic treatment), while it presented as mild in four patients. Anti-TNFα therapy was totally withdrawn in case 1. In case 2, the treatment was halted for 3 months then switched to another TNFα blocker, and case 3 was switched to another anti-TNFα treatment. The treatment was sustained in the other 3 patients (cases 4, 5, and 6).

Conclusions TNFα blockers are very effective agents in the treatment of psoriasis, but it is interesting that the same molecules can, paradoxically, induce psoriasis. The occurrence of anti-TNFα-induced psoriasis in six out of 514 patients suggests that the incidence of this adverse reaction is, in fact, as not low as presumed in the literature. In some cases, a severe course of psoriasis may limit the use of these agents.     

Serum interleukin-6 level is associated with response to infliximab in ulcerative colitis

Objectives: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection.

Materials and method: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period.

Results: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p?=?.012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio?=?0.72; 95% confidence interval, 0.54–0.96; p?=?.027) was independently associated with response to infliximab.

Conclusions: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.     

Serum IL-6, TNFα and CRP levels in Greek colorectal cancer patients: Prognostic implications

AIM: The significance of preoperative serum IL-6, TNFαand CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their prognostic significance.METHODS: The IL-6, TNFα and CRP levels were measured in 74 CRC patients and the relationships between their elevation s and both the clinicopathological factors and prognosis of patients were investigated. Serum concentrations of human IL-6 and TNFα were determined by enzyme-linked immunosorbent assay (ELISA). CRP was measured by an immunoturbinometric method.RESULTS: Median IL-6, TNFα and CRP levels weresignificantly higher in CRC patients than in normal controls.High levels of serum IL-6, TNFα and CRP were correlated with larger tumor size. Furthermore, high IL-6 and high CRP levels were associated with reduced overall survival.CONCLUSION: Serum IL-6, TNFα and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNFα in CRC needs to be further investigated.     

The role of thrombopoietin in post-operative thrombocytosis

Thrombopoietin (Tpo), the main regulator of thrombocytopoiesis, is a probable candidate to play a role in the increase in platelet counts that is frequently seen after surgery. In the current study, serial blood samples of patients that underwent major surgery were analysed with respect to Tpo kinetics, platelet turnover and inflammatory cytokines. Platelet Tpo content and plasma Tpo levels rose before platelet counts increased, suggesting that Tpo was indeed responsible for the elevation in platelet counts. In addition, an increase in interleukin 6 (IL-6) levels, but not in IL-11 and tumour necrosis factor alpha levels, was seen before the rise in Tpo concentration. In vitro, IL-6 was shown to enhance Tpo production by the HepG2 liver cell line. Thus, increased Tpo levels after surgery, possibly resulting from enhanced Tpo production under the influence of IL-6 or other inflammatory cytokines, are involved in an enhanced thrombocytopoiesis.     

Proinflammatory and atherogenic activity of monocytes in type 2 diabetes

Cytokines secreted by the monocyte–macrophage system play a key role in the progression of atherosclerotic lesions in Type 2 diabetes. The objectives of this study were to assess the influence of cytokine gene expression in monocytes from patients with Type 2 diabetes on direct markers of endothelial injury with regard to clinically manifest atherosclerosis.MethodsMonocytes from 58 patients with Type 2 diabetes and from 22 age-matched healthy volunteers of a control group were isolated in order to assess expression of tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-8 and IL-10 cytokines (RTPCR, Applied Biosystems). Thrombomodulin concentration was determined using a Diagnostica Stago Immunoenzymatic assay, and circulating endothelial cell numbers were assayed using immunofluorescence studies with CLB-HEC19 antibodies.ResultsIn 28 patients, TNFα expression in monocytes was observed. In these patients, as compared to those with undetectable levels of this cytokine's expression, higher hemoglobin A_1c (P=.012) and thrombomodulin (P=.005) concentrations were found. IL-8 expression was determined in 36 patients. Higher expression of TNFα (P=.048) and IL-8 (P=.049) was detected in patients with peripheral arterial disease in contrast to those free from this complication.ConclusionTNFα and IL-8 play a significant role in the proatherogenic activity of monocytes in Type 2 diabetes. The TNFα-connected activity of monocytes may directly determine endothelial dysfunction and injury. The location of atherosclerosis should be taken into account in the assessment of the proinflammatory activity of peripheral blood monocytes.     

Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice

BackgroundThe role of Kupffer cell interleukin (IL)-1 in non-alcoholic steatohepatitis development remains unclear.AimsTo evaluate the role of Kupffer cell IL-1α, IL-1β or IL-1 receptor type-1 (IL-1R1) in steatohepatitis.MethodsC57BL/6 mice were irradiated and transplanted with bone marrow-derived cells from WT, IL-1α−/−, IL-1β−/− or IL-1R1−/− mice combined with Kupffer cell ablation with Gadolinium Chloride, and fed atherogenic diet. Plasma and liver triglycerides and cholesterol, serum alanine aminotransferase (ALT), liver histology and expression levels of inflammatory genes were assessed.ResultsThe ablation and replacement of Kupffer cells with bone marrow-derived cells was confirmed. The atherogenic diet elevated plasma and liver cholesterol, reduced plasma and liver triglycerides and increased serum ALT levels in all groups. Steatosis and steatohepatitis were induced, but without liver fibrosis. A reduction in the severity of portal inflammation was observed only in mice with Kupffer cell deficiency of IL-1α. Accordingly, liver mRNA levels of inflammatory genes encoding for IL-1α, IL-1β, TNFα, SAA1 and IL-6 were significantly lower in mice with Kupffer cell deficiency of IL-1α compared to WT mice.ConclusionSelective deficiency of IL-1α in Kupffer cells reduces liver inflammation and expression of inflammatory cytokines, which may implicate Kupffer cell-derived IL-1α in steatohepatitis development.     

Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis

 We wished to test whether thrombopoietin (TPO) is entirely regulated by receptor binding or if other factors may play a role in the mechanism of TPO regulation. Therefore, we analyzed the TPO serum levels in 43 patients with reactive (secondary) thrombocytosis and in 37 with myeloproliferative thrombocytosis. Thrombocytosis was defined as a platelet level greater than 440×10⁹/l. Forty-two patients (98%) with reactive thrombocytosis had high concentrations of IL-6 correlating with elevated C-reactive protein levels. Twenty-three patients (53%) in this group had TPO serum concentrations of more than 300 pg/ml (normal: below 300 pg/ml). Only nine patients (24%) with myeloproliferative thrombocytosis had TPO serum levels above normal range, whereas 28 patients (76%) had normal levels of TPO. No correlation between the TPO serum levels and the concentrations of IL-6 or EPO was established. The other investigated thrombopoietic cytokines (IL-3, IL-11, GM-CSF) were unmeasurable; therefore, a correlation could not be assessed. We conclude that TPO concentrations are not strictly inversely related to platelet count. TPO serum levels are elevated especially in a considerable percentage of patients with reactive thrombocytosis, arguing for the existence of additional mechanisms of TPO regulation. Received: February 28, 1998 / Accepted: August 18, 1998     

Serum levels of thrombopoietin and stem cell factor in acute leukemia patients with chemotherapy-induced cytopenia and complicating infections

Thrombopoietin (Tpo) and stem cell factor (SCF) are growth factors for megakaryocyte progenitor cells and can also modulate platelet function. We have characterized variations in serum levels of these two cytokines in acute leukemia patients undergoing intensive chemotherapy. Compared with healthy controls, serum Tpo levels were significantly increased prior to consolidation chemotherapy, and serum levels were correlated to peripheral blood platelet counts. Serum Tpo levels increased when the patients developed chemotherapy-induced cytopenia, and a further increase was observed during complicating bacterial infections. In contrast to Tpo, SCF serum levels in leukemia patients did not differ from healthy controls neither before chemotherapy nor during the period of chemotherapy-induced cytopenia. Serum levels of Tpo (and possibly SCF) may influence thrombopoiesis and/or platelet functions in patients undergoing intensive chemotherapy for acute leukemia.     

Serum levels of thrombopoietin and stem cell factor in acute leukemia patients with chemotherapy-induced cytopenia and complicating infections

Thrombopoietin (Tpo) and stem cell factor (SCF) are growth factors for megakaryocyte progenitor cells and can also modulate platelet function. We have characterized variations in serum levels of these two cytokines in acute leukemia patients undergoing intensive chemotherapy. Compared with healthy controls, serum Tpo levels were significantly increased prior to consolidation chemotherapy, and serum levels were correlated to peripheral blood platelet counts. Serum Tpo levels increased when the patients developed chemotherapyinduced cytopenia, and a further increase was observed during complicating bacterial infections. In contrast to Tpo, SCF serum levels in leukemia patients did not differ from healthy controls neither before chemotherapy nor during the period of chemotherapy-induced cytopenia. Serum levels of Tpo (and possibly SCF) may influence thrombopoiesis and/or platelet functions in patients undergoing intensive chemotherapy for acute leukemia.     

Serum interleukin-6 and survivin levels predict clinical response to etanercept treatment in patients with established rheumatoid arthritis

Objectives: To investigate the correlation of nine potential biomarkers with clinical response to etanercept (ETN) therapy in establish rheumatoid arthritis (RA) patients.

Methods: Seventy-three patients with established RA were enrolled in the prospective cohort study. Sixty-nine of 73 cases were included into final analysis for response after 24-week ETN therapy. Serum expression of nine studied proteins was measured by enzyme-linked immunosorbent assay (ELISA). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-21, IL-34, RANKL, survivin, and COMP were selected as candidate biomarkers.

Results: Serum IL-6 level was increased in responders than in nonresponders at baseline, p?=?.034; to the contrary, serum survivin level was decreased in responders, p?=?.009. Receiver operating characteristic (ROC) curve illuminated the combination of IL-6 and survivin expressions could predict clinical response with a high AUC 0.875, 95% CI: 0.771–0.976. Furthermore, we found the combination of IL-6 high expression and survivin low expression increased the responding possibility to nearly 20-fold (OR 19.687, 95% CI: 4.087–94.839, p?<?.001) compared to IL-6 low or survivin high expression by univariate analysis. However, only survivin low expression (p?=?.002) and CRP (p?=?.014) high expression were independent predictive factors for achieving clinical response, while IL-6 lack independent predictive value (p?=?.267).

Conclusions: Comprehensive measurement of IL-6 and survivin in serum could be served as a convincing biomarker for clinical response in ETN-treated patients with established RA.