Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.

BACKGROUND: The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial. AIMS: This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls. METHODS: A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored. RESULTS: In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels. CONCLUSION: In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.

Serum levels of IL-9 and IL-11 serve as predictors for the occurrence of early neurologic deterioration in patients with cerebral infarction.

BACKGROUND AND AIM: Early neurological deterioration (END) is a common complication of cerebral infarction and a significant contributor to poor prognosis. Our study aimed to investigate the predictive value of interleukin-9 (IL-9) and interleukin-11 (IL-11) in relation to the occurrence of END in patients with cerebral infarction. MATERIALS AND METHODS: 102 patients with cerebral infarction and 64 healthy controls were collected. Patients were categorized into two groups based on the development of END following admission: the END group (n = 44) and the non-END group (n = 58). Enzyme-linked immunosorbent assay was used to determine the serum levels of IL-9, IL-11, and BDNF. RESULTS: Serum IL-9 was higher and IL-11 lower in the END group than those in the non-END group (P < 0.01). IL-9 correlated positively with NIHSS score (r = 0.627) and infarction volume (r = 0.686), while IL-11 correlated negatively (r = -0.613, -0.679, respectively). Logistic regression identified age, NIHSS score, and IL-9 as risk factors (P < 0.01), and IL-11 as protective (P < 0.01). Combined IL-9 and IL-11 had an ROC curve area of 0.849. BDNF correlated negatively with IL-9 (r = -0.703) and positively with IL-11 (r = 0.711). CONCLUSION: Serum IL-9 and IL-11 levels can predict the occurrence of END in patient with cerebral infarction and are correlated with serum BDNF levels.

Rehabilitation Training Can Significantly Increase the Serum IL-11 Levels and Improve the Prognosis in Ischemic Stroke Patients.

We aimed to explore the expression of IL-11 in ischemic stroke patients and its correlation with rehabilitation training and prognosis. The present randomized control study recruited ischemic stroke patients who were admitted during March 2014 to November 2020. All patients underwent computer tomography (CT) and magnetic resonance imaging (MRI) examination. All patients were randomly divided into two groups, including rehabilitation training (RT) group and control group. The patients in the RT group were received rehabilitation training within 2 days after the vital signs were stable while control group received routine nursing. The serum interleukin- (IL-) 11 levels were measured by enzyme-linked immunosorbent assay (ELISA) when patients were just hospitalized and 6 h, 24 h, 48 h, 72 h, and 90 h after treatment. Demographic, clinical statistics, imaging data, and the National Institutes of Health Stroke Scores (NIHSS) were recorded. The modified Rankin Scale (mRS) scores were measured after 90 days treatment to assess the prognosis of ischemic patients. The serum IL-11 levels of the RT group elevated more quickly during the study time compared with the control group. In addition, the NIHSS and mRS scores of ischemic stroke patients in the RT group were significantly lower than that in the control group. The NIHSS score, the proportion receiving rehabilitation training, and the levels of IL-11, triglyceride (TG), and high-density leptin cholesterol (HDLC) of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than that in the mRS score ≤ 2 group. However, the serum IL-11 levels of ischemic stroke patients were obviously decreased in the mRS score ≥ 3 group. IL-11 could be a potential diagnostic biomarker of poor prognosis of ischemic stroke patients. Furthermore, IL-11, NIHSS score, and rehabilitation training were the risk factors for poor prognosis of ischemic stroke patients. This study demonstrated that the ischemic stroke patients in the RT group had higher serum IL-11 levels and better prognosis. This study might provide a new approach to improve the prognosis of patients with ischemic stroke. This trial is registered with ChiCTR-PNR-16007706.

IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFß-mediated activation of dermal fibroblasts.

OBJECTIVES: Interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with activation of human dermal fibroblasts (HDFs) from patients with SSc or controls. METHODS: We measured serum IL11 levels in volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches that we combined with molecular and cellular phenotyping. RESULTS: In patients with SSc, serum IL11 levels are elevated as compared with healthy controls. All transforming growth factor beta (TGFß) isoforms induced IL11 secretion from HDFs, which highly express IL11 receptor α-subunit and the glycoprotein 130 (gp130) co-receptor, suggestive of an autocrine loop of IL11 activity in HDFs. IL11 stimulated ERK activation in HDFs and resulted in HDF-to-myofibroblast transformation and extracellular matrix secretion. The pro-fibrotic action of IL11 in HDFs appeared unrelated to STAT3 activity, independent of TGFß upregulation and was not associated with phosphorylation of SMAD2/3. Inhibition of IL11 signalling using either a neutralizing antibody against IL11 or siRNA against IL11RA reduced TGFß-induced HDF proliferation, matrix production and cell migration, which was phenocopied by pharmacological inhibition of ERK. CONCLUSIONS: These data reveal that autocrine IL11-dependent ERK activity alone or downstream of TGFß stimulation promotes fibrosis phenotypes in dermal fibroblasts and suggest IL11 as a potential therapeutic target in SSc.

Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure.

BACKGROUND: Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF. METHODS: The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events. RESULTS: Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations. CONCLUSIONS: Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection.

BACKGROUND: Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). METHODS: Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. RESULTS: Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. CONCLUSION: IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD.

Interleukin 11 is upregulated in preeclampsia and leads to inflammation and preeclampsia features in mice.

Preeclampsia is a dangerous pregnancy complication, which is often associated with fetal growth restriction and can have serious life-long effects for both mother and baby. While the establishment of the placenta in the first trimester is the sentinel event in the development of preeclampsia little is known of the critical mechanisms of placentation that lead to the syndrome. Locally produced inflammatory cytokines are thought to play a role in the development of preeclampsia. This review summarizes the evidence that interleukin 11 is dysregulated in preeclampsia and contributes to the initiation of preeclampsia via effects on placentation. It discusses the benefits and drawbacks of targeting IL11 as a novel treatment option for preeclampsia.

Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in paediatric sickle cell disease.

BACKGROUND: Alteration in the concentration of inflammatory cytokines may contribute to pathogenesis in sickle cell anaemia (SCA). Vitamin D may suppress pro-inflammatory cytokines and enhance anti-inflammatory cytokines. OBJECTIVE: To compare steady state levels of pro-and anti-inflammatory cytokines of Nigerian SCA children with age- and sex-matched healthy controls, and determine the relationship with 25-hydroxyvitamin-D (25-OHD). Effects of three months of vitamin D supplementation on cytokines of SCA children with suboptimal 25-OHD were also evaluated. METHODS: Serum 25-OHD, IL-1ß, 2, 6, 8, 11, 12, 13, 17, 18 of 95 SCA children and 75 matched controls were determined using HPLC. The 12 SCA children with suboptimal 25-OHD received 2000IU of vitamin D daily for 3months, and their post supplementation cytokines and 25-OHD levels were compared with the baseline values. RESULTS: IL-2, 6, 8, 12, 17 and 18 were higher in SCA children than the controls (p≤0.001), but no significant variation in IL-11 and 13 (p=0.131 and 0.057 respectively). Patients with suboptimal serum 25-OHD had higher IL-6, 8 and 18 (p=0.003, 0.010 and 0.002 respectively) and lower levels of IL-11 (p=0.005). Significant positive treatment effects were observed: post-supplementation, serum 25-OHD increased by 23.3ng/mL, p<0.001; proinflammatory cytokines IL-2, 6, 8, 17 and 18 (p<0.001) were reduced and anti-inflammatory cytokine IL-11 was increased, p<0.001. CONCLUSIONS: Suboptimal 25OHD is associated with enhanced levels of pro-inflammatory markers in children with SCA. Three months of daily vitamin D supplementation reversed the trend. Hence; Vitamin D supplementation may reduce the inflammatory milieu and serve as an anti-inflammatory agent in the management of SCA.

Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH).

To study the changes in serum interleukin-11 (IL-11), tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) expressions following hypertensive intracerebral hemorrhage (HICH), and explore their associations with disease severity and prognosis. Serum IL-11, TNF-α, and VEGF levels after 1, 3, 7, and 14 days after HICH were assayed using enzyme-linked immunosorbent assay (ELISA), and neurological deficit score (NDS) were recorded at admission and discharge for 99 HICH cases. Then 45 healthy controls were included and assayed for serum IL-11, TNF-α, and VEGF levels. Serum IL-11, TNF-α, and VEGF levels were higher in HICH patients than healthy controls (all P < 0.05). TNF-α was higher at the 3rd day following disease onset than other time points (all P < 0.05), while IL-11 and VEGF peaked at the 7th day and dropped below baseline values at the 14th day (all P < 0.05). Serum IL-11 was positively correlated with TNF-α (r = 0.70, P < 0.05) and VEGF (r = 0.72, P < 0.05). Serum TNF-α was positively correlated with VEGF (r = 0.46, P < 0.05). Serum IL-11, TNF-α, and VEGF were associated with disease severity in HICH patients. Patients with more severe disease tended to have higher NDS at admission, and higher IL-11, TNF-α, and VEGF during treatment were associated with higher NDS at discharge. Serum IL-11, TNF-α, and VEGF may involve in the pathophysiology of HICH, thus IL-11, TNF-α, and VEGF may be prognostic factors for post HICH neurologic damage.

Serum CD121a (Interleukin 1 Receptor, Type I): A Potential Novel Inflammatory Marker for Coronary Heart Disease.

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1ß, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79-2.72], 2.67 (95% CI: 1.47-4.84), and 4.71 (95% CI: 2.65-8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70-3.14), 2.25 (95% CI: 1.10-4.62), and 4.39 (95% CI: 2.19-8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1ß levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.

IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.

Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase of the disease, which may provide valuable insight into the molecular mechanisms of the initiation of the autoimmune response in MS. Our results introduce IL-11 as a new cytokine that plays a role in the autoimmune response in the early phase of the disease. IL-11 is the highest upregulated cytokine in the sera and cerebrospinal fluid from CIS patients, which is also increased in patients with clinically definitive relapsing-remitting MS in comparison with healthy control subjects. Serum IL-11 levels are significantly increased during clinical exacerbations in comparison with remissions in the same patients. CD4(+) cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11(+)CD4(+) cells is significantly increased in CIS patients in comparison with healthy control subjects. Furthermore, we have identified IL-11 as a new Th17-promoting cytokine, because it induces a differentiation of naive CD4(+) T cells into Th17 cells, as well as expansion of Th17 memory cells. Because the Th17 cytokines IL-17F, IL-21 and TNF-α, and TGF-ß induce differentiation of naive cells in the IL-11-secreting CD4(+) cells, we propose that cross-talk between IL-11(+)CD4(+) and Th17 cells may play a role in the inflammatory response in relapsing-remitting MS.

[Differential expressions of serum cytokines in cognitive dysfunction patients after colorectal surgery].

OBJECTIVE: To evaluate the serum levels of cytokines in postoperative cognitive dysfunction (POCD) patients having received colorectal surgery. METHODS: Eighty patients who had received colorectal surgery were enrolled in the study based on the defined inclusion and exclusion criteria. Cognitive function was assessed on day 1 before operation and day 7 after operation using a battery of neuropsychological tests. Serum levels of 120 cytokines were measured at two time points (day 1 before surgery and 4 hours after surgery) using high-throughput cytokine screening. Serum interleukin 6 (IL-6), IL-11, IL-17, Fas, methyl-accepting chemotaxis protein 3 (MCP3), myeloid progenitor inhibitory factor-1 (MPIF-1), macrophage inflammatory protein 3 alpha (MIP-3α), brain-derived neurotrophic factor (BDNF) were determined by ELISA. RESULTS: Seventy-seven patients completed both neurocognitive tests and blood samples collection. Nineteen cases were diagnosed with POCD at 7 days after surgery. The age, ASA classification and diabetes incidence of POCD patients were significantly higher and the education level was lower than those in patients without POCD. Serum IL-17, Fas, MIP-3α levels were higher and leptin was lower when compared with non-POCD patients at 1 day before surgery. Serum IL-6, IL-11, IL-17, MCP3, MPIF-1, MIP-3α levels were higher and BDNF was lower when compared with non-POCD group at 4 hours after surgery. In POCD group, serum IL-6, IL-17, MCP3 and MPIF-1 levels at 4 hours postoperatively were higher when compared with ones at 1 day preoperatively. In non-POCD group, serum IL-6 and IL-17 at 4 hours postoperatively were higher while Fas and BDNF were lower when compared with ones at 1 day preoperatively. CONCLUSION: Serum cytokines IL-6, IL-11, IL-17, Fas, MPIF-1, MIP-3α, MCP3, leptin, BDNF were found to display differential expressions in POCD patients after colorectal surgery.

Neurologic sequela in a patient with galactosemia potentially mediated by interleukin-11 dysfunction.

A 16-year-old galactosemic patient, homozygous for the 5.5-kb gene deletion, suffered severe neurologic regression following streptococcal infection. Since the gene deletion includes the promoter of interleukin-11a receptor involved in neuronal apoptosis, we questioned whether this patient had no interleukin-11a receptor activity-resulting in neuronal toxicity during septicemia. We hypothesized that interleukin-11 levels would be elevated because of a loss of feedback induced by the absent interleukin-11Ra receptor complex. To assess this, we compared interleukin-11 levels in the proband and 2 of his siblings with the same genetic deletion, to age-matched controls. No differences were found in interleukin-11 levels between groups. Our study was not carried out during acute infective states, when the disrupted immunoregulation triggered by sepsis is relevant, and is thus limited. In conclusion, although interleukin-11 was not chronically elevated in individuals with galactosemia and 5.5-kb gene deletion, data do not rule out potential interleukin-11 dysfunction during acute infection.

Complex pattern of interleukin-11-induced inflammation revealed by mathematically modeling the dynamics of C-reactive protein.

Inflammation underlies many diseases and is an undesired effect of several therapy modalities. Biomathematical modeling can help unravel the complex inflammatory processes and the mechanisms triggering their emergence. We developed a model for induction of C-reactive protein (CRP), a clinically reliable marker of inflammation, by interleukin (IL)-11, an approved cytokine for treatment of chemotherapy-induced thrombocytopenia. Due to paucity of information on the mechanisms underlying inflammation-induced CRP dynamics, our model was developed by systematically evaluating several models for their ability to retrieve variable CRP profiles observed in IL-11-treated breast cancer patients. The preliminary semi-mechanistic models were designed by non-linear mixed-effects modeling, and were evaluated by various performance criteria, which test goodness-of-fit, parsimony and uniqueness. The best-performing model, a robust population model with minimal inter-individual variability, uncovers new aspects of inflammation dynamics. It shows that CRP clearance is a nonlinear self-controlled process, indicating an adaptive anti-inflammatory reaction in humans. The model also reveals a dual IL-11 effect on CRP elevation, whereby the drug has not only a potent immediate influence on CRP incline, but also a long-term influence inducing elevated CRP levels for several months. Consistent with this, model simulations suggest that periodic IL-11 therapy may result in prolonged low-grade (chronic) inflammation post treatment. Future application of the model can therefore help design improved IL-11 regimens with minimized long-term CRP toxicity. Our study illuminates the dynamics of inflammation and its control, and provides a prototype for progressive modeling of complex biological processes in the medical realm and beyond.

Plasma interleukin-11 (IL-11) levels have diagnostic and prognostic roles in patients with pancreatic cancer.

Interleukin-11 (IL-11) affects inflammation, motility, and invasion in cancer. Here, we investigated the clinical significance of plasma IL-11 (IL-11p) levels in patients with pancreatic cancer. We enrolled 44 patients with pathologically confirmed diagnoses of pancreatic cancer into this study (median age at diagnosis, 68 years; range, 42-86 years), along with 30 age- and sex-matched healthy controls and 3 patients with pancreatitis complicated with pancreatic cysts and 15 patients with early pancreatitis. Median baseline IL-11p levels of patients with pancreatic cancer were significantly higher than that of the healthy controls (P < 0.001), as were those of the 15 patients with early pancreatitis. IL-11p levels presented high diagnostic accuracy for pancreatic cancer (area under the curve (AUC), 0.901; sensitivity, 97.7%; specificity, 70.0%). Age, sex, lesion site, disease stage, serum dehydrogenase, alkaline phosphatase, γ-glutamyltransferase, and white blood cells, platelets, and hemoglobin levels did not correlate with IL-11p concentrations (P>0.05), but patients with distant metastases had lower median IL-11p values than did patients without distant metastases (P=0.043). Patients with IL-11p higher than the median level (43.2 pg/mL) had better prognoses than those with lower values (P=0.004), particularly as IL-11p concentration increased to ≥ 50 pg/mL (P=0.001). IL-11p concentration correlated with overall survival (≥ median IL-11p, 10 months;

Optimal attenuation of experimental autoimmune encephalomyelitis by intravenous immunoglobulin requires an intact interleukin-11 receptor.

BACKGROUND: Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however its mechanism of action remains elusive. Recent work has shown that interleukin-11 (IL-11) mRNAs are upregulated by IVIg in MS patient T cells. Both IVIg and IL-11 have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The objective of this study was to determine whether the protective effects of IVIg in EAE occur through an IL-11 and IL-11 receptor (IL-11R)-dependent mechanism. METHODS: We measured IL-11 in the circulation of mice and IL-11 mRNA expression in various organs after IVIg treatment. We then followed with EAE studies to test the efficacy of IVIg in wild-type (WT) mice and in mice deficient for the IL-11 receptor (IL-11Rα-/-). Furthermore, we evaluated myelin-specific Th1 and Th17 responses and assessed spinal cord inflammation and demyelination in WT and IL-11Rα-/- mice, with and without IVIg treatment. We also examined the direct effects of mouse recombinant IL-11 on the production of IL-17 by lymph node mononuclear cells. RESULTS: IVIg treatment induced a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and a prominent increase of IL-11 mRNA expression in the liver. Furthermore, we found that IL-11Rα-/- mice, unlike WT mice, although initially protected, were resistant to full protection by IVIg during EAE and developed disease with a similar incidence and severity as control-treated IL-11Rα-/- mice, despite initially showing protection. We observed that Th17 cytokine production by myelin-reactive T cells in the draining lymph nodes was unaffected by IVIg in IL-11Rα-/- mice, yet was downregulated in WT mice. Finally, IL-11 was shown to directly inhibit IL-17 production of lymph node cells in culture. CONCLUSION: These results implicate IL-11 as an important immune effector of IVIg in the prevention of Th17-mediated autoimmune inflammation during EAE.

Stability-indicating capillary zone electrophoresis method for the assessment of recombinant human interleukin-11 and its correlation with reversed-phase liquid chromatography and biossay.

A stability-indicating capillary zone electrophoresis (CZE) method was validated for the analysis of recombinant human interleukin-11(rhIL-11) using rupatadine fumarate, as internal standard (IS). A fused-silica capillary, (50 µm i.d.; effective length, 40 cm) was used at 25°C; the applied voltage was 20 kV. The background electrolyte solution consisted of 50 mmol L(-1) sodium dihydrogen phosphate solution at pH 3.0. Injections were performed using a pressure mode at 50 mbar for 45 s, with detection by photodiode array detector set at 196 nm. Specificity and stability-indicating capability were established in degradation studies, which also showed that there was no interference of the excipients. The method was linear over the concentration range of 1.0-300 µg mL(-1) (r(2)=0.9992) and the limit of detection (LOD) and limit of quantitation (LOQ) were 0.2 µg mL(-1) and 1.0 µg mL(-1), respectively. The accuracy was 100.4% with bias lower than 1.1%. Moreover, the in vitro cytotoxicity test of the degraded products showed significant differences (p<0.05). The method was applied for the content/potency assessment of rhIL-11 in biopharmaceutical formulations, and the results were correlated to those of a validated reversed-phase LC method (RP-LC) and an TF-1 cell culture assay, showing non-significant differences (p>0.05). In addition the CZE and RP-LC methods were applied for the analysis of rhIL-11 in human plasma. Therefore, the proposed alternative method can be applied to monitor stability, to assure the batch-to-batch consistency and quality of the bulk and finished biotechnology-derived medicine.

Unusual early-stage pancreatic sarcomatoid carcinoma.

Sarcomatoid carcinoma of the pancreas (SCP) is a very rare pathological type of carcinoma that usually has a poor prognosis. Its pathogenesis has not been elucidated. We herein report a case of an early-stage SCP involving successful treatment and a good prognosis. The patient was a 48-year-old Chinese man with a 5-mo history of vague abdominal pain. Ultrasonography revealed a 93 mm × 94 mm × 75 mm mass of mixed echogenicity in the tail of the pancreas. Laboratory test results were within the normal range, with the exception of an obviously increased pretreatment neuron-specific enolase level. The plasma transforming growth factor (TGF)ß1 and interleukin-11 levels were obviously increased according to enzyme-linked immunosorbent assay. Microscopically, the excised tumor tissue comprised cancer cells and mesenchymal cells. Immunohistochemical analysis was positive for α-1-antichymotrypsin, pan-cytokeratin, cytokeratin 19, cytokeratin 8/18, and vimentin and negative for CD68 and lysozyme. The pathogenetic mechanism of this case shows that TGFß1 may regulate the epithelial-to-mesenchymal transition in SCP. With early eradication of the tumor and systemic therapy, this patient has been alive for more than 3 years without tumor recurrence or distant metastasis. This case is also the first to show that TGFß1 may regulate the epithelial-to-mesenchymal transition in early-stage SCP.

Association of TLR4 Gene rs2149356 polymorphism with primary gouty arthritis in a case-control study.

BACKGROUND: The toll-like receptor (TLR)4-interleukin1ß (IL1ß) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1ß signaling pathway molecules expression. METHODS AND FINDINGS: The rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1ß were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1ß were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR = 1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted OR = 1.96). TLR4 mRNA and IL1ß were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively). CONCLUSIONS: The TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.

Expression of IL-2 and IL-11 and its significance in patients with ankylosing spondylitis.

OBJECTIVE: To explore the expression of IL-2 and IL-11 and its significance in patients with ankylosing spondylitis (AS). METHODS: A total of 48 active AS patients in our hospital and 40 normal control subjects were selected in our study. Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI), ESR and CRP expression levels were compared before treatment, 12 h after treatment and 24 h after treatment. IL-2 and IL-11 expression were also compared between these two groups. RESULTS: The BASDAI score, BASFI score and BASMI score of the AS patients before treatment significantly decreased compared with those 12 weeks and 24 weeks after treatment (P<0.05). ESR and CRP levels of the AS patients 12 weeks and 24 weeks after treatment significantly decreased compared with those before treatment (P<0.05). Difference was significant in serum IL-2 and IL-11 levels between 12 weeks and 24 weeks after treatment and before treatment (P<0.05). And no statistically significance was observed for serum IL-2 and IL-11 levels between normal control group and those of patients in AS group 24 weeks after treatment (P>0.05). Pearson's linear-correlation analysis showed that serum IL-2 level had a positive correlation with BASDAI, BASFI, BASMI, ESR and CRP (r=0.661,0.547,0.474,0.362,0.416, P<0.05) and serum IL-11 level had a negative correlation with BASDAI, BASFI, BASMI, ESR and CRP (r=-0.629, -0.412, -0.422, -0.387, -0.408, -0.315, P<0.05). CONCLUSIONS: Serum levels of IL-2 in active AS patients significantly increase and will decrease after treatment. However, serum levels of IL-11 significantly decrease and will increase after treatment, which indicates that serum IL-2 has a positive correlation with the degree of AS and serum IL-11 has a negative correlation with the degree of AS, both of which are correlated closely with the onset of AS.