The role of interleukin­7 serum level as biological marker in breast cancer: a cross­sectional, observational, and analytical study.

BACKGROUND: The important role that the immune system plays in malignant diseases is well known. The action of interleukin-7 (IL-7) as a cytokine has been observed in many cellular processes, both in normal cells of the immune system and in some cancer cells. The aim of this study has been to explore whether there is any elevation of interleukin-7 serum levels in early invasive breast cancer (EIBC) patients in comparison with healthy controls. In addition, the correlation between the IL-7 serum level and the histopathological characteristics of the tumor has been evaluated. METHODS: This cross-sectional, observational, and analytical study included 213 consecutive patients with EIBC (113 from Croatia and 100 from Kosovo) and 62 healthy participants as the control group (30 from Croatia and 32 from Kosovo). Blood samples have been taken from patients confirmed with breast cancer (BC) by biopsy, prior to surgical intervention and other oncological treatments, as well as from healthy participants. A serum IL-7 level has been measured, using the "Sandwich" ELISA Immunoenzyme test. In addition, after the surgical intervention, histopathological specimen examinations and immunohistochemistry have been performed and analyzed. The differences in the distribution of the numerical variables have been analyzed with the Mann-Whitney U test and Kruskal-Wallis ANOVA test. Correlations have been tested with Pearson coefficients. A P-value < 0.05 has been accepted as statistically significant. RESULTS: The serum level of IL-7 in EIBC patients was significantly higher than in control cases (P 0.001). Patients with invasive lobular carcinoma (ILC) seem to have a lower IL-7 serum level compared to other histological subtypes, and the difference has been significant (P = 0.043). There has been no correlation between IL-7 serum level and histopathological characteristics of the tumor, with neither age nor menopausal status of the patients. CONCLUSIONS: Noting the significant increase in the IL-7 serum level in the EIBC patients as compared to the healthy control group, the use of IL-7 as a potential diagnostic indicator for BC, as well as in the follow-up of the patients after treatment, can be assumed. The lack of correlation with tumor size, lymph node metastasis, and all other histopathological characteristics of the tumor questions its use as a prognostic indicator.

Serial measurement of cytokines strongly predict COVID-19 outcome.

PURPOSE: Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. METHODS: In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. RESULTS: At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). CONCLUSION: Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

Interleukin-7 Is Associated with Clinical and Pathological Activities in Immunoglobulin A Nephropathy and Protects the Renal Proximal Tubule Epithelium from Cellular Fibrosis.

OBJECTIVE: Diagnosis of immunoglobulin A nephropathy (IgAN) requires the evaluation of renal biopsy specimens. However, renal biopsy is an invasive procedure and is not frequently performed for various reasons. Thus, recognized noninvasive biomarkers for predicting IgAN progression are urgently needed. METHODS: In the present study, we included 86 IgAN patients with renal biopsy from June 2015 to May 2016 and had their plasma interleukin-7 (IL-7) level measured with ELISA. The association between the plasma IL-7 level and clinico-pathological characteristics was analyzed. Immunohistochemical staining was used to assay the in situ expression of IL-7 in vivo. Western blotting was performed to examine the production of extracellular matrix, p-mTOR and the markers of autophagy under the treatment of IL-7 after TGF-ß1 stimulation in renal tubular epithelial cells. RESULTS: IL-7 was significantly decreased in patients with IgAN compared to healthy subjects (2.3077 vs. 8.6294 pg/mL, P<0.0001). There was a significant difference in the plasma IL-7 level between tubular atrophy/interstitial fibrosis T0 and T2 classes (P=0.0064). A lower plasma IL-7 value in patients at the time of biopsy indicated a poor renal outcome. In addition, IL-7 was over-expressed in renal tubular epithelial cells and significantly attenuated transforming growth factor ßl-induced extracellular matrix production by suppression of cellular autophagy via activation of mTOR1 signaling. CONCLUSION: These results suggested that IL-7 might be a noninvasive biomarker for predicating IgAN. It protected renal proximal tubular epithelial cells from cellular fibrosis by inhibiting autophagy via mTORl signaling.

Thymopoiesis, Alterations in Dendritic Cells and Tregs, and Reduced T Cell Activation in Successful Extracorporeal Photopheresis Treatment of GVHD.

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Sixteen pediatric HSCT patients were recruited: 6 with ECP-treated aGVHD, 5 without aGVHD, and 5 with aGVHD treated with corticosteroids only. Thymopoiesis was evaluated by measuring naive T cells, TRECs, IL-7, and T cell receptor repertoire diversity. Regulatory T cell (Treg) enumeration and function and dendritic cell (DC) enumeration and phenotype were analyzed using flow cytometry. T cell transcriptome analysis was performed on ECP patients after treatment and responders pre- and post-treatment. Four ECP responders demonstrated thymic-dependent T cell recovery, and superior median naïve T cell numbers at 8 and 12 months post-HSCT compared to the aGVHD corticosteroid group. Increased Tregs and Treg suppressive function, reduced cDC/pDC and DC co-stimulatory marker expression in ECP responders suggest upregulated peripheral tolerance; these findings were not observed in partial responders. Responder post-ECP CD3+ T cell transcriptional profile demonstrated 3333 downregulated and 364 upregulated genes, with significant downregulation of ERRα and GαS pathways, and reduced expression of pro-inflammatory and adhesion proteins.Thymic function improves with successful ECP treatment. ECP reduces T cell activation and impacts peripheral tolerance via DCs and Tregs. Differences in thymic recovery, DC, and Treg cellular patterns and the T cell transcriptome were observed between ECP responders and partial responders and require further validation and investigation in additional patients.

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort.

PURPOSE: Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia. MATERIALS AND METHODS: A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/µL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively. RESULTS: Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. -0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months. CONCLUSION: IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

Plasma Oncostatin M, TNF-α, IL-7, and IL-13 Network Predicts Crohn's Disease Response to Infliximab, as Assessed by Calprotectin Log Drop.

BACKGROUND: Cytokines emerge as possible biomarkers of response in Crohn's disease (CD). We aimed to determine the plasmatic cytokine profiles of active CD patients who started infliximab (IFX) treatment and their capacity to predict the response to IFX. METHODS: A total of 30 active CD patients receiving an induction therapy of IFX were enrolled in the study. Peripheral blood samples pretreatment were collected. Concentrations of 15 cytokines were measured by Luminex technology. Responses to IFX were evaluated by the drop in fecal calprotectin based on its logarithm-transformed values. A random forest (RF) predictive model was used for data analyses. RESULTS: Samples of 22 patients were analyzed. The RF model ranked the following cytokines as the top predictors of the response: tumor necrosis factor alpha (TNFα), interleukin (IL)-13, oncostatin M (OSM), and IL-7 (p < 0.005). Partial dependency plots showed that high levels of IL-13 pretreatment, low TNFα levels, and low IL-7 levels were associated with a favorable IFX response. Increased levels of OSM and TNFα predicted unfavorable responses to IFX. CONCLUSIONS: We here show that a log drop in calprotectin strongly correlates with clinical parameters and it can be proposed as a useful objective clinical response predictor. Plasma TNFα, IL-13, Il-7, and OSM network could predict CD response to IFX before induction therapy, as assessed by calprotectin log drop.

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. RESULTS: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. CONCLUSION: Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.

Impact of ART on dynamics of growth factors and cytokines in primary HIV infection.

Antiretroviral treatment (ART) of Primary HIV Infection (PHI) has demonstrated virological and immunological benefits. The effect of early ART during PHI on the level of growth factors and chemokines modulating immune cell functions remains to be established. The aim of our work was to analyze the dynamics of 27 cytokines, chemokines and growth/regulation factors in plasma of HIV infected patients treated during PHI. Patients with PHI (n = 43) were enrolled before, 24 and 48 weeks after therapy initiation. Quantification of soluble immune mediators was performed in plasma from HIV infected patients and healthy donors (HD, n = 7) by Luminex technology. The cytokines profile was strongly perturbed in primary HIV infected patients when compared to healthy donors (HD). After 48 weeks of ART, some of these factors were restored to HD level (IL-2, IL-5, IL-7, IL-9, IL12p70, TNFα) while others persisted higher than HD (IL-6, IL-10, IL-13). Interestingly, a subset of chemokines, such as IL-8, MCP-1, RANTES and CCL27, and growth factors such as HGF, SCF and GM-CSF, increased during ART, reaching values significantly higher than HD after 48 weeks. Moreover, the G-CSF and MIP-1ß soluble mediators were persistently altered and showed an inverse correlation with the CD4/CD8 T cell ratio. The increase of chemokines with antiviral activity and of growth factors with hematopoietic and immunomodulatory properties may have beneficial effects. Other studies are mandatory to evaluate the effects of long lasting levels of these factors to clarify their possible role in the context of protection/pathogenesis.

Alterations in the Levels of Growth Factors in Adolescents with Major Depressive Disorder: A Longitudinal Study during the Treatment with Fluoxetine.

Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods. All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results. All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions. To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD.

Human Umbilical Cord Blood Serum/Plasma: Cytokine Profile and Prospective Application in Regenerative Medicine.

The concentrations of cytokines and growth factors in human umbilical cord blood serum and plasma samples were measured by multiplex analysis. It was found that in comparison with peripheral blood serum of adult donors, umbilical cord blood serum and plasma contain significantly higher concentrations of the most studied molecules including IL-4, 5, 6, 7, 10 and 15, MCP-1, SCF, and SDF, as well as growth factors directly involved in the processes of regeneration (G-CSF, HGF, PDGF-BB, and VEGF). Thus, umbilical cord blood plasma and especially serum are a rich source of cytokines and growth factors with anti-inflammatory, anti-apoptotic, and angiogenic effects and can be used in various fields of regenerative medicine.

Interleukin-7, T helper 1, and regulatory T-cell activity-related cytokines are increased during the second trimester of healthy pregnancy compared to non-pregnant women.

PROBLEM: Healthy pregnancy is associated with a physiologic increase in inflammatory responses. The objective of this study was to assess changes in plasma cytokines associated with uncomplicated pregnancy. METHOD OF STUDY: To examine these changes, plasma levels of immune response mediators from healthy gravidas (N = 115, gestation weeks 23-30) were compared with those from healthy non-pregnant women (N = 42). Comparisons were performed using multiplex analysis for Th1 activity-related cytokines (IFN-γ, IL-2, sIL-2Rα, IL-12[P70], and IL-27), Th2 activity-related cytokines (IL-4, IL-5, and IL-13), other immune response mediators (GM-CSF, IL-1ß, sIL-1RI, IL-6, IL-8, IL-15, IL-17A, IL-17F, IL-21, IL-22, IL-23, TGFß1, TGFß2, TGFß3, and TNFα), regulatory T cell-related cytokines (IL-10 and sTNFRII), adipokines (adiponectin, leptin, PAI-1, and resistin), chemokines (IP-10, MCP-1, and MIP-1ß), and hematopoietic growth factor IL-7. RESULTS: Multivariate linear regression models showed increased levels of IL-7, Th1-, and Treg activity-related cytokines and decreased levels of adipokines and chemokines in healthy gravidas compared with healthy non-pregnant women. Additionally, season of the year, age, pre-pregnancy body mass index, and HLA-DR/DQ genotypes for type 1 diabetes risk showed different and sometimes reciprocal influence on cytokine levels. CONCLUSION: Our study stresses the importance of profiling immune response mediators during pregnancy to better understand the effect of healthy pregnancy on cytokine levels.

Local and Systemic IL-7 Concentration in Gastrointestinal-Tract Cancers.

BACKGROUND AND OBJECTIVES: Interleukin-7 (IL-7) is exploited in cancer immunotherapies although its status in solid tumors is largely unknown. We aimed to determine its systemic and local concentrations in esophageal (EC), gastric (GC), and colorectal (CRC) cancers. MATERIALS AND METHODS: IL-7 was immunoenzymatically measured in paired surgical specimens of tumors and tumor-adjacent tissue (n = 48), and in the sera of 170 individuals (54 controls and 116 cancer patients). Results: IL-7 was higher in tumors as compared to noncancerous tissue in all cancers (mean difference: 29.5 pg/g). The expression ratio (tumor to normal) was 4.4-fold in GC, 2.2-fold in EC, and 1.7-fold in CRC. However, when absolute concentrations were compared, the highest IL-7 concentrations were in CRC, both when tumor and noncancerous tissue were analyzed. In CRC tumors, IL-7 was 2 and 1.5 times higher than in EC and GC tumors. In noncancerous CRC tissue, IL-7 was 2.3- and 2.8-fold higher than in EC and GC. IL-7 overexpression was more pronounced in Stage 3/4 and N1 cancers as a result of decreased cytokine expression in noncancerous tissue. Tumor location was a key factor in determining both local and systemic IL-7 concentrations. Serum IL-7 in CRC and EC was higher than in controls, GC, and patients with adenocarcinoma of gastric cardia (CC), but no significant correlation with the disease advancement could be observed. Conclusions: IL-7 protein is overexpressed in EC, GC, and CRC, but concentrations differ both in tumor and tumor-adjacent tissue with respect to tumor location. More advanced cancers have lower IL-7 concentrations in the immediate environment of the tumor. At the systemic level, IL-7 is elevated in CRC and EC, but not CC or GC. IL-7 dependence on the location of the primary tumor should be taken into account in future IL-7-based immunotherapies. Functional studies explaining a role of IL-7 in gastrointestinal cancers are needed.

Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice.

The immune system encompasses acquired and innate immunity that matures through interaction with microenvironmental components. Cytokines serve as environmental factors that foster functional maturation of immune cells. Although NOD/SCID/IL2rgKO (NSG) humanized mice support investigation of human immunity in vivo, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune function. To study the roles of human cytokines in human acquired and innate immune cell development, we created NSG mice expressing hIL-7 and hIL-15. Although hIL-7 alone was not sufficient for supporting human NK cell development in vivo, increased frequencies of human NK cells were confirmed in multiple organs of hIL-7 and hIL-15 double knockin (hIL-7xhIL-15 KI) NSG mice engrafted with human hematopoietic stem cells. hIL-7xhIL-15 KI NSG humanized mice provide a valuable in vivo model to investigate development and function of human NK cells.

Th2 and Th17 Induce Dry Skin in a Mouse Model of Arthritis.

Skin dryness is a characteristic of rheumatoid arthritis (RA) model mice. However, the mechanism underlying the induction of dry skin by RA is unclear. We hypothesized that T helper (Th)2 and Th17 cells mediate this process. A mouse model of DBA/1JJmsSlc collagen-induced arthritis was treated with Th2 or Th17 cell inhibitor, and transepidermal water loss (TEWL) and the expression of markers associated with allergic reaction and inflammation were evaluated. TEWL and plasma levels of thymic stromal lymphopoietin, interleukin (IL)-6 and -17, and tumor necrosis factor (TNF)-α were increased in the arthritis mouse model compared to that in control mice. Administration of Th2 cell inhibitor abolished the increase in TEWL, IL-6, and TNF-α levels, whereas Th17 cell inhibitor reversed TEWL and decreased IL-17 level. Th2 and Th17 cells contribute to the induction of dry skin, but via distinct mechanisms.

Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.

Correlation between IL-7 genomic protein methylation level and acute myeloid leukemia.

OBJECTIVE: To detect Interleukin-7 (IL-7) gene methylation status and transcription level in leukemia cells of peripheral blood of patients with Acute Myelocytic Leukemia (AML) and in the cell lines (HL-60, HL-60/ADM, SKM-1) of AML and myelodysplastic syndrome (MDS), and explore its relationship with the pathogenesis of AML. PATIENTS AND METHODS: A total of 55 AML patients (AML group) and 30 healthy adults (Healthy group) from June 2015 to June 2018 were enrolled in this study. The genomic DNA of leukemia cells in peripheral blood was extracted. The methylation-specific PCR (MSP) method was used to detect the methylation rate of the IL-7 gene in peripheral blood of AML group and Health group. Meanwhile, the methylation level of the IL-7 gene leukemia cell lines HL-60/ADM, HL-60, and MV4-11 and SKM-1 were detected in vitro. At the same time, the expression level of IL-7 in peripheral blood was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The methylation rate of IL-7 gene in peripheral blood of the AML group and Healthy group was 72.7% (40/55) vs. 3.3% (1/30) (p<0.01); IL-7 gene methylation occurred in HL-60/ADM, HL-60, MV4-11 and SKM-1 cell lines. IL-7 gene methylation appears in peripheral blood leukemia cells and AML and MDS cell lines of AML patients. CONCLUSIONS: The expression of IL-7 in peripheral blood of patients with AML is significantly decreased, suggesting that this phenomenon is related to the pathogenesis of AML.

Interleukin-15 and Interleukin-7 are the Major Cytokines to Maintain Endometriosis.

OBJECTIVE: The objective of this study was to evaluate cytokines related to natural killer and T-regulatory cells in endometriotic lesions, peritoneal fluid (PF) and the peripheral blood (PB) of patients with deep infiltrative endometriosis. STUDY DESIGN: A case-control study was conducted in a tertiary referral hospital. Sixty-four consecutive patients after laparoscopy were divided into 2 groups: with endometriosis (Group A - n = 32) and without endometriosis (Group B - n = 32). MAIN OUTCOME MEASURES: Interleukin (IL)-2, IL-4, IL-7, IL-10, IL-12, IL-15, transforming growth factor ß1, and IFNγ concentration was measured using a LuminexTM multiplex suspension bead array. Tissues from endometriotic lesions of patients with endometriosis and from eutopic endometrium were evaluated, as well as PF and PB of all patients. RESULTS: Compared to the other analyzed groups, IL-15 concentration was significantly higher in the ectopic endometrium and IL-7 in the eutopic endometrium of the endometriosis group (p < 0.05). Compared to endometriosis group, IFNγ, IL-7, and IL-15 were observed to be significantly higher in the PF of the control group, and IL-10 was lower in the control group (p < 0.05). In PB, compared to endometriosis group, IL-4, IL-10, IL-12, IL-15, and IFNγ concentrations were significantly higher in the control group (p < 0.05). CONCLUSIONS: Our hypothesis is that deep endometriosis is a disease out of control. This disease's nature is of progression and invasion of adjacent structures, and proof of this disease state is the disorganized secretion of cytokine regulation and inflammation, which seem to be among the factors responsible for the maintenance of the disease.

Higher Interleukin-7 serum concentrations in patients with cystic fibrosis correlate with impaired lung function.

BACKGROUND: Patients with cystic fibrosis (CF) are highly susceptible to infection and colonization of pulmonary epithelia. Repeated and chronic infections may affect disease course and efficacy of host immune protection. Higher Interleukin (IL)-7 serum levels, indicating impaired T-cell response to IL-7, have been described for chronic viral and mycobacterial infections. METHODS: Time course measures of IL-7 serum concentrations in patients with CF (n = 164; n = 78 for the second time point) and healthy controls (n = 60) were done. CF patients were characterized for disease severity parameters as well as infection status and association with IL-7 serum levels was determined. RESULTS: CF patients had significantly higher IL-7 serum concentrations as compared to healthy controls (9.79 pg/ml, IQR 6.76-13.6 versus 4.55 pg/ml, IQR 2.76-9.51, p < .001). IL-7 serum levels were negatively correlated with individual CF patient's BMI (r = -0.19, p = .021) and a tendency of increased IL-7 levels in Staphylococcus aureus infected CF patients was found. Linear regression of multiple parameters revealed significant negative correlation of FEV1%pred with IL-7 serum concentrations in patients with CF (ß-coefficient: -0.04, 95% confidence interval [-0.08; -0.003], p = .034). Time course analyses after 1 year +/- 6 months showed increased IL-7 serum levels (time point 1:9.26 pg/ml, IQR 6.94-13.12 time point 2:10.86 pg/ml, IQR 9.14-14.76, p = .016) that correlated negatively with decreased FEV1%pred during CF disease course. CONCLUSIONS: High IL-7 serum levels were found in CF patients and correlated with impaired lung function during CF disease course. As a candidate biomarker of T-cell dysfunction, higher IL-7 serum level may also indicate worsened immune competence of patients with CF.

The perioperative dynamics of IL-7 following robot-assisted and open colorectal surgery.

Interleukin-7 is critical for T-cell development and displays antimicrobial and antitumor properties. It is referred to as a "critical enhancer of protective immunity". However, there is no information on interleukin-7 dynamics following colorectal surgery. Moreover, although robot-assisted surgery is gaining popularity, data on the immune response to it is almost non-existent. In this prospective non-randomized case-control study we found interleukin-7 dynamics to differ following robot-assisted and open approach and to affect postoperative immunity. Linear increases were seen in the robotic group while a cubic pattern with a maximum at 8 h in the open one. Low preoperative interleukin-7 was associated with developing surgical site infection. In turn, higher preoperative interleukin-7 was associated with preserved immune function: less pronounced drop in lymphocyte count and higher Δlymphocyte/Δneutrophil ratio in patients undergoing robotic surgery. The changes in other cytokines, namely, interleukin-12(p70), TNFα, interferon-γ, and interleukin-10 were independently associated with interleukin-7 dynamics. In turn, relative changes in interleukin-7 were independent predictors of changes in interferon-γ, key cytokine of favourable Th1 immune response. Taken together, we demonstrated different perioperative dynamics of interleukin-7, which may contribute to favourable outcomes following robotic colorectal surgery including lower incidence of surgical site infections, milder surgery-induced lymphopenia, and beneficial interferon-γ dynamics.

The effect of occupational chronic lead exposure on the complete blood count and the levels of selected hematopoietic cytokines.

Associations among lead exposure, blood morphology, and cytokines influencing hematopoiesis are still inconclusive. Therefore, the objective of the present study was to demonstrate whether workers chronically exposed to lead demonstrate changes in complete blood count (CBC) parameters associated with altered levels of selected cytokines influencing hematopoiesis. The study covered 80 male subjects employed in the zinc-lead works in Miasteczko Slaskie. The subjects were divided into two groups: control group (24 healthy administration workers without a history of occupational exposure to lead compounds) and lead exposed group (56 subjects exposed to lead compounds in their work environment). The values of HTC, MCV, MCH, RDW-CV, PDW, and LMR were significantly lower in the exposed group than in the controls by 3%, 5%, 3%, 4%, 15%, and 47%, respectively. However, the levels of MCHC and MPV were higher in the exposed group than in the controls by 3% and 11%, respectively. Analogically, the values of MXD and MXD% were also significantly higher by 118% and 70%, respectively. The concentration of IL-7 was significantly higher in the exposed group compared to the controls by 143%. In this study, chronic lead exposure in the occupational setting at levels <50 µg/dl does not affect RBC count and hemoglobin level but decreases MCV and hematocrit. Similarly, chronic lead toxicity does not affect WBC count but alters proportions of different types of leukocytes with significant increase of MXD count associated with elevated level of IL-7. Oppositely to a short-term lead exposure, chronic lead exposure elevates MPV and does not alter PLT count.