Median Concentrations Of IL-10 Research Articles

Serum Level Kinetic of Key Cytokines in Newly Diagnosed Lymphoma Patients during First Line Treatment: Correlation with PET/CT Scan Results and Treatment Outcome

Background: Cytokines are soluble proteins that play a key role in mediating and regulating inflammation and immune responses. Further, they are involved in lymphoid development and differentiation, as well as in lymphoid tumorigenesis. Aim of the present study was to verify if the serum-cytokine levels could be an early marker of treatment response. With this purpose, we analyzed the serum concentration kinetic of key cytokines in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) pts comparing it with PET/CT scan results and treatment outcome. Patients and Methods: After Ethic Committee approval, we start to enroll lymphoma pts treated at Modena Cancer Center. Until now, 29 patients entered the study, including 12 pts with DLBCL, 11 with FL, and 6 with HL. DLBCL lymphoma were treated with R-CHOP and FL patients with R-CVP or R-Benda or R-CHOP, while HL patients with ABVD + ABVD or BEACOP following indications of intermediate PET. A panel of eight serum cytokines/chemokines (IL6, IL2, IL8, IL10, IFNγ, TNFα, CXCL10/IPI10, CCL17/TARC) was analyzed using the Simple Plex system (Protein Simple, San Jose, CA, USA) according to the manufacturer's recommendations. Serum samples were collected at the day of staging (PET-0), at the day of intermediate PET (I-PET) and at the day of end treatment PET (EOT-PET). Samples were analyzed in duplicate. Continuous variables were compared by Mann-Whitney test and categorical variables by Chi2 test. Matched data were analyzed by paired Wilcoxon or Friedman test. Statistical significance was defined as p < 0.05. Results: The median age of all 29 pts was 60 yr (range 21-86), and 65 % were male. Patients with HL were younger (50 yr) than pts with FL (61 yr) and DLBCL (68 yr). In all 29 pts, median concentration of IL10, IL6, TNFα at EOT-PET decreased in comparison with the levels at PET-0, while IFNγ and IPI10 increased. IL8 increased in DLBCL and in HL, while decreased in FL. IL2 levels did not show relevant changes. No statistically significant differences were found between the concentrations of these cytokines at PET-0 and EOT-PET. The mean serum TARC level at PET-0 were 854 pg/mL (range 130-5829), 1209 pg/mL (range 134-6903) and 8327 pg/mL (range 6488-10885) in DLBC, FL and HL pts, respectively. At EOT-PET the mean concentration of TARC were 562 pg/mL (range 130-854) (p=0.49), 989 pg/mL (range 134-6903) (p=0.74), 591 pg/mL (range 353-932) (p=0.03 ) in DLBCL, FL and HL pts, respectively. In HL patients, TARC values were significantly lower at I-PET with a mean of 525 pg/mL (range 210-1062) compared to PET-0 (p=0.016), with a p value along the 3 timepoint =0.009. EOT-PET and I-PET, evaluated by Deauville score shows that almost all patients achieved CR at the end of treatment: 11 out of 12 DLBCL pts have a Deauville score between 1 and 3, as well as all FL and HL pts. Only 1 DLBCL patient had a Deauville score of 4 at the end of treatment, achieving CR after further radiotherapy. Conclusion: Our study, despite the limitations due to the small number of pts enrolled to date, shows that the concentrations of cytokines/chemokines, with the exception of TARC, do not undergo significant changes, before and after first-line therapy. The TARC values, on the other hand, correlate well with the results of PET/CT and therefore also with the response to therapy in all subtypes of lymphoma. This correlation is statistically significant in pts with HL. TARC assessment could therefore become a useful, inexpensive and easy to determine predictive marker of response to therapy and may be important for determining treatment strategy in lymphoma patients. Further, the TARC levels assessed during the follow-up could be early markers of relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Array analysis for T-cell associated cytokines in gingival crevicular fluid: Identifying altered profiles associated with periodontal disease status

ObjectiveCytokine networks regulate innate and adaptive immune responses, which in turn are recognised to direct the progression or arrest of periodontal disease. This study aimed to compare the profile of seven cytokines, implicated in regulating T-cell networks, in gingival crevicular fluid (GCF) samples with differing classification of periodontal status. MethodsGCF samples were collected from patients with strong clinical evidence for chronic periodontitis, aggressive periodontitis, gingivitis or no gingival inflammation. Cytokines IL-6, IFN-ɣ, IL-4, IL-2, IL-17 A, IL10 and TNFα were measured in each sample using a commercial cytometric bead array assay. Descriptive statistics were used to indicate central tendency, data scatter and analysis of variance for each cytokine concentrations between respective patient groups. Heat maps with dendrograms were produced to visualise hierarchical clustering and trends within the data. ResultsMedian concentrations for all cytokines analysed were highest for gingivitis samples and lowest for aggressive periodontitis samples. The median concentration of IL-6 in gingivitis samples was observed to be 10.5 fold higher (˜17,300 pg/μl) than IL-6 in aggressive periodontitis samples (˜1600 pg/μl). Median concentrations of IL-10, IL-17 A and TNFα were also 2–2.2 fold higher in gingivitis samples compared to aggressive periodontitis. ConclusionsDescriptive statistical analysis noted raised concentrations of IL-6, IL-17 A and TNFα associated with gingivitis; pro-inflammatory cytokines usually associated with periodontal tissue destruction, including bone. Our results would suggest that these cytokines can additionally provide protective roles in preventing progression to advanced forms of periodontal disease. Potential for how these cytokines contribute to providing this role is discussed. Clinical significanceDefining the roles for the many cytokines involved in the pathogenesis of periodontal disease is far from complete. Consequently the results of this study serve to evidence proposals that cytokines can exhibit both pro- and anti-inflammatory effects, which is dependent on the signalling environment within which they exist and the antagonizing or modifying actions of other cytokines. Whilst future research is necessary to explore mechanistic action, our study contributes new knowledge suggesting that IL-6 and IL-17 A can provide roles in stabilising the lesion to limit disease progression, which does not preclude alternative roles in promoting periodontal bone loss in advanced forms of disease progression, which is also documented in the literature.

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies

BackgroundAlthough immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases.Case PresentationThe study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers.ConclusionsElevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid concentrations of sHLA-G have no diagnostic value in differentiating between ovarian malignancies and endometriomas.

IL10 and IL10:IL6 Ratio in CSF Is Useful at Diagnosis but Also in the Assessment of Therapeutic Response in Patients with Primary Central Nervous System Lymphoma (PCNSL)

Reliable biomarkers of primary central nervous system lymphoma (PCNSL) are needed to support the magnetic resonance imaging (MRI) findings especially when the cerebral biopsy cannot be performed for pathologic examination. Biomarkers are also needed to optimize the assessment of therapeutic response, which so far relies only on gadolinium uptake on MRI, although large discrepancies of outcomes are observed in patients in complete remission assessed by MRI criteria.The aim of the present study was to evaluate the diagnostic and prognostic values of the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 and of the IL-10:IL-6 ratio in patients with diffuse large B-cell type (DLBCL) PCNSL, at time of diagnosis and after treatment.IL-10 and IL-6 levels were measured in 120 patients with DLBCL-PCNSL and 36 control patients with other brain tumor or inflammatory neurologic diseases, using the quantitative Cytometric Bead Array® technique (human IL-10 CBA kit and human IL-6 CBA kit; BD BiosciencesTM) on a FACSCanto II cytometer (BD BiosciencesTM) according to the manufacturer’s recommendations. Serial measures of cytokines were performed in 57 patients. The IL-10:IL-6 ratio distinguishes PCNSL from other neurological diseases. Using a cutoff level of 1.0, the sensitivity and specificity are 94% and 80% respectively. Meningeal dissemination defined by cytological examination and/or flow cytometry analysis, is significantly associated with a higher IL-10 concentration (417 pg/ml vs 22 pg/ml; p = 0.0024) and a higher IL-10:IL-6 ratio (32 vs 6 ; p = 0.0011). Previous treatment with corticosteroids significantly reduces the IL-10:IL-6 ratio (ratio=7.6 with corticosteroids vs 21.9 without corticosteroids; p= 0.02). With a median follow-up of 25 months, the pre-therapeutic concentration of IL-10 has no prognostic value on overall and progression free survivals. After treatment, the median concentration of IL-10 is significantly decreased in patients entering complete (CR) or partial response (PR) compared to non-responder patients (median = 35.9 pg/ml and 235.5 pg/ml respectively, p = 0.01). We demonstrate for the first time that among patients in CR or PR (as per MRI criteria), a persistent detectable IL-10 level in CSF (> 2,5 pg/ml) has an impact on the progression free survival (1 year PFS: 21.2 % vs 53.6%; p= 0,004) (figure 1).Our study shows that IL-10:IL-6 ratio can be used as a diagnostic biomarker for PCNSL of DLBCL type . Analysis will be done to determine the cut off values of IL10 and IL-10:IL-6 ratio in a predictive model of meningeal dissemination. We also provide evidence that IL-10 concentration may be useful to complete the assessment of therapeutic response in PCNSL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Interleukin-6, interleukin-10 and interleukin-12 in vaginal fluid from women with bacterial vaginosis

There has been a recent recognition on the influence of local vaginal immunity on the acquisition of vulvovaginal disorders and their adverse consequences. Variations in local immune responses seem to play an important role in susceptibility to different vaginal infections as well as to the likelihood of recurrences. Bacterial vaginosis (BV), the most frequent vaginal disorder in most populations, is enigmatic in that the etiology is unknown, recurrences are common and vaginal inflammation is absent. We investigated the influence of BV on the vaginal concentration of the pro-inflammatory cytokine interleukin (IL)-12, the pleiotropic cytokine IL-6 and the anti-inflammatory cytokine IL-10 in non-pregnant women. Vaginal lavage samples were obtained from 45 patients with BV and from 46 asymptomatic controls. The supernatant fractions were examined for IL-6, IL-10 and IL-12 by commercial ELISAs. Analysis of the cytokine levels in the two groups was by the Mann-Whitney test. IL-6 concentrations varied considerably among women in the BV and control groups but the median levels were almost identical. The median concentrations of IL-10 and IL-12 were uniformly low in both groups but median levels were not statistically different. The marked alteration in the vaginal bacterial flora that is characteristic of BV does not result in enhancement or inhibition of the vaginal levels of IL-6, IL-10 and IL-12. Mechanisms to explain this striking lack of immune system variation remain to be determined.

Maternal Serum Interleukin‐10, Interleukin‐2 and Interleukin‐6 in Pre‐Eclampsia and Eclampsia

The aim of the study was to investigate and compare the concentrations of interleukin (IL)-2, IL-6, and IL-10 in serum of women with mild pre-eclampsia, severe pre-eclampsia, eclampsia, and normotensive pregnancy. A total of 69 consecutive cases, 38 mild pre-eclampsia, 20 severe pre-eclampsia, 11 eclampsia, and 20 normotensive controls were included in this study. Serum IL-2, IL-6, and IL-10 levels were determined using enzyme-linked immunosorbent assay method. Gestational age (P = 0.210) and body mass index (P = 0.214) between the groups were similar. The mean concentration of serum IL-2 and IL-6 were not different between the groups (P = 0.261, P = 0.141 respectively). The median concentrations of serum IL-10 in patients with mild and severe pre-eclampsia were similar (P < 0.282) and was significantly lower than those of controls (P < 0.001) and patients with eclampsia (P < 0.001). In patients with eclampsia, the median concentration of IL-10 was significantly higher than that of all other groups (P < 0.001 for each comparison). Pre-eclampsia is associated with a deficiency serum IL-10. High serum IL-10 is correlated with the presence of eclampsia.

Different cytokine profiles in patients with a history of gangrenous or phlegmonous appendicitis

Appendicitis is one of the most common and costly acute abdominal states of illnesses. Previous studies suggest two types of appendicitis which may be different entities, one which may resolve spontaneously and another that progresses to gangrene and perforation. Gangrenous appendicitis has a positive association to states of Th1 mediated immunity whereas Th2 associated immune states are associated with lower risk of appendicitis. This study investigated the inflammatory response pattern in patients previously appendicectomized for gangrenous (n = 7), or phlegmonous appendicitis (n = 8) and those with a non-inflamed appendix (n = 5). Peripheral blood mononuclear cells were analysed with ELISPOT analysis for number of spontaneous or antigen/mitogen stimulated IFN-gamma, IL-4, IL-10 and IL-12 secreting cells or with ELISA for concentration of spontaneous or antigen/mitogen stimulated IFN-gamma, IL-5 and IL-10. Spontaneously IL-10 secreting cells/100,000 lymphocytes were increased in the gangrenous group compared to the phlegmonous group (P = 0.015). The median concentration of IL-10 secreted after Tetanus toxoid (TT)-stimulation were higher in the gangrenous group and the control group, than the phlegmonous group (P = 0.048 and P = 0.027, respectively). The median concentration of TT induced IFN-gamma secretion was higher for the gangrenous group compared to both the phlegmonous group and the control group (P = 0.037 and P = 0.003). Individuals with a history of gangrenous appendicitis demonstrated ability to increased IL-10 and IFN-gamma production. The increased IFN-gamma may support the notion of gangrenous appendicitis as an uncontrolled Th1 mediated inflammatory response and increased IL-10 may speculatively indicate the involvement of cytotoxic cells in the progression to perforation.