Median Interleukin-8 Levels Research Articles

Impact of baseline serum IL-8 on metastatic hormone-sensitive prostate cancer outcomes in the Phase 3 CHAARTED trial (E3805).

The immunosuppressive cytokine interleukin- 8 (IL-8), produced by tumor cells and some myeloid cells, promotes inflammation, angiogenesis, and metastasis. In our discovery work, elevated serum IL-8 at androgen deprivation therapy (ADT) initiation portended worse overall survival (OS). Leveraging serum samples from the phase 3 CHAARTED trial of patients treated with ADT +/- docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), we validated these findings. Two hundred and thirty-three patients had serum samples drawn within 28 days of ADT initiation. The samples were assayed using the same Mesoscale Multiplex ELISA platform employed in the discovery cohort. After adjusting for performance status, disease volume, and de novo/metachronous metastases, multivariable Cox proportional hazards models assessed associations between IL-8 as continuous and binary variables on OS and time to castration-resistant prostate cancer (CRPC). The median IL-8 level (9.3 pg/ml) was the a priori binary cutpoint. Fixed-effects meta-analyses of the discovery and validation sets were performed. Higher IL-8 levels were prognostic for shorter OS (continuous: hazard ratio [HR]2.2, 95% confidence interval [CI]: 1.4-3.6, p = .001; binary >9.3: HR 1.7, 95% CI: 1.2-2.4, p = .007) and time to CRPC (continuous: HR2.3, 95% CI: 1.6-3.3, p < .001; binary: HR 1.8, 95% CI: 1.3-2.5, p < .001) and independent of docetaxel use, disease burden, and time of metastases. Meta-analysis including the discovery cohort, also showed that binary IL-8 levels >9.3 pg/ml from patients treated with ADT alone was prognostic for poorer OS (HR1.8, 95% CI: 1.2-2.7, p = .007) and shorter time to CRPC (HR1.4, 95% CI: 0.99-1.9, p = .057). In the phase 3 CHAARTED study of men with mHSPC at ADT initiation, elevated IL-8 portended worse survival and shorter time to castration-resistant prostate cancer independent of docetaxel administration, metastatic burden, and metachronous versus de novo metastatic presentation. These findings support targeting IL-8 as a strategy to improve mHSPC outcomes.

Neutrophil elastase in cervical fluid in women with short cervical length

ObjectiveThe aim of the study was to determine the relationships between short cervical length (CL) and levels of cervical fluid neutrophil elastase (NE), secretory leukocyte protease inhibitor (SLPI), and interleukin 8 (IL-8) in the second trimester of pregnancy of women who underwent ultrasound-indicated cervical cerclage. Materials and methodsCL of <25 mm or cervical funneling were included in the short CL group (n = 26) and the normal CL group (n = 22) included women who had CL of ≥25 mm and had no cervical funneling in women between 17 + 0 and 24 + 6 weeks of gestation. Levels of NE, SLPI, and IL-8 were measured by using enzyme-linked immunosorbent assay kits. Mann–Whitney U tests and Spearman's correlation analysis were used for statistical analyses. ResultsCompared with the normal CL group, the short CL group had significantly higher median NE levels (P < 0.001) and higher, though not significant, median IL-8 levels by approximately three times (2107.0 vs. 798.3 pg/mL, P = 0.132). The median SLPI levels in cervical fluid was similar between the two groups (107.6 vs. 103.2 ng/mL, P = 0.499). Short CL had a significant correlations with cervical fluid NE levels (r = −0.475, P = 0.001). ConclusionIncreased cervical fluid NE associated with cervical shortening in second trimester of pregnancy, whereas cervical fluid SLPI had constant levels.

Significant Decrease in Plasma Levels of D-Dimer, Interleukin-8, and Interleukin-12 After a 12-Month Treatment with Rosuvastatin in HIV-Infected Patients Under Antiretroviral Therapy.

Statins have shown anti-inflammatory and immune-modulatory properties in both general and HIV-infected population, but their effect on plasma D-dimer levels is controversial and it has not been investigated to date in HIV-positive patients. The aim of our study was to assess the effect of rosuvastatin on D-dimer and other serum inflammation markers among these subjects. Prospective, cohort study of HIV-1-infected adult patients receiving a stable combination antiretroviral therapy (cART), who started a lipid-lowering therapy with rosuvastatin (10 mg daily) and were followed up for at least 12 months. The primary endpoint was the change at month 12 in the median plasma concentration of D-dimer. The secondary endpoints included the variation in median plasma levels of these inflammatory biomarkers: interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12). Sixty-two patients were enrolled in the study, and the endpoints were available for 54 subjects. After 12 months, a significant decrease in median plasma concentration of D-dimer was observed (-21.4%; interquartile range [IQR], -35.5; -4.2; p = .029). With regard to the inflammatory biomarkers, a significant decrease in median levels of IL-8 (-24.6%; IQR, -30.8; -1.8; p = .012) and IL-12 (-18.7%; IQR, -25.8; +2.5; p = .033) was also observed. Rosuvastatin led to a significant reduction in serum lipid values and showed a good tolerability profile. Our findings show that a 12-month treatment with rosuvastatin associated with an effective cART can significantly decrease the plasma levels of D-dimer, IL-8, and IL-12, and suggest a potential role for this statin to reduce activated coagulation and systemic inflammation among HIV-infected persons.

A cohort study comparing the serum levels of pro- or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects.

The factors influencing the presence or absence of pain in sciatica secondary to disc herniation remain incompletely understood. We hypothesized that the imbalance in inflammatory cytokines is implicated in the generation of pain. In our study, serum levels of pro-inflammatory and anti-inflammatory cytokines were investigated among patients with severe sciatica; the serum levels were compared with those of patients with mild sciatica and healthy subjects. In this prospective study, blood protein levels of the pro-inflammatory cytokines, namely, interleukin-6 (IL-6), interleukin-8 (IL-8),and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines, namely, interleukin-4 (IL-4) and interleukin-10 (IL-10), of 58 patients with severe sciatica, 50 patients with mild sciatica, and 30 healthy control subjects were analyzed through ELISA. Physical and mental health symptoms were determined using the Oswestry Disability Index (ODI) and short form-36 (SF-36) questionnaire. Spearman rank correlation coefficient was also determined to calculate the correlation between the scores obtained from the questionnaires and the serum levels of cytokines. IL-6 protein was detected in the three groups and median levels were about 1.5 times higher in patients with severe sciatica than the mild sciatica group (p=0.02) and the controls (p=0.03). Median levels of IL-8 in sciatica patients were higher than those of the healthy controls (p=0.001 for severe sciatica, p=0.02 for mild sciatica). The TNF-α protein values were approximately twofold higher in the severe sciatica group than in the mild sciatica group (p<0.01) and in the healthy control group (p<0.01). Median levels of IL-4 were about 2.5-fold higher in mild sciatica (p<0.01) and about twofold higher in patients with severe sciatica (p=0.012) when compared with controls. Median protein levels of IL-10 showed a trend to be higher in patients with mild sciatica compared with severe sciatica (p<0.01) and with healthy controls (p<0.01). ODI was significantly correlated with IL-6 (r=0.394, p=0.013), TNF-α (r=0.629, p<0.001), and IL-10 (r=-0.415, p=0.009). ODI was not significantly correlated with IL-4 (r=-0.174, p=0.29) and IL-8 (r=-0.133, p=0.418). These findings support our hypothesis that sciatica pain is accompanied by the imbalance in inflammatory cytokines.

Evaluation of IL-8 nasal lavage levels and the effects of nasal involvement on disease severity in patients with stable chronic obstructive pulmonary disease.

Interleukin 8 (IL-8) is used to evaluate the severity of inflammation in the airways. The aim of this study was to evaluate patients with chronic obstructive pulmonary disease (COPD) for the presence of upper respiratory tract involvement by questioning patients regarding nasal symptoms and by measuring levels of IL-8 in nasal lavage material. A total of 47 COPD patients and 23 healthy controls were enrolled in this study. Pulmonary function tests were performed for all participants who were asked to complete a Sinonasal Outcome Test-20 (SNOT-20) questionnaire on the same day, as a measure of quality of life. Median IL-8 level in nasal lavage specimens of COPD patients with stable disease was higher than that of healthy controls. An increase in cigarette pack-years was significantly associated with an increase in nasal IL-8 levels. Similarly, IL-8 levels correlated positively with stage of COPD. A significant link between number of visits to the emergency department and stage of disease was observed. Patients with COPD had a significantly higher mean SNOT-20 severity score compared to healthy controls. Proper management of sinonasal disease may help to decrease the number of COPD attacks and consequently improve quality of life.

Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain.

The objective was to assess the accuracy of novel and traditional biomarkers in patients with suspected appendicitis as a function of duration of symptoms. This was a prospective cohort study, conducted in a tertiary care emergency department (ED). The authors enrolled children 3 to 18 years old with acute abdominal pain of less than 96 hours and measured serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP), white blood cell (WBC) count, and absolute neutrophil count (ANC). Final diagnosis was determined by histopathology or telephone follow-up. Trends in biomarker levels were examined based on duration of abdominal pain. The accuracy of biomarkers was assessed with receiver operating characteristic (ROC) curves. Optimal cut-points and test performance characteristics were calculated for each biomarker. Of 280 patients enrolled, the median age was 11.3 years (interquartile range [IQR] = 8.6 to 14.8), 57% were male, and 33% had appendicitis. Median IL-6, median CRP, mean WBC count, and mean ANC differed significantly (p < 0.001) between patients with nonperforated appendicitis and those without appendicitis; median IL-8 levels did not differ between groups. In nonperforated appendicitis, median IL-6, WBC, and ANC levels were maximal at less than 24 hours of pain, while CRP peaked between 24 and 48 hours. In perforated appendicitis, median IL-8 levels were highest by 24 hours, WBC count and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain. The WBC count appeared to be the most useful marker to predict appendicitis in those with fewer than 24 or more than 48 hours of pain, while CRP was the most useful in those with 24 to 48 hours of pain. In this population, the serum levels and accuracy of novel and traditional biomarkers varies in relation to duration of abdominal pain. IL-6 shows promise as a novel biomarker to identify children with appendicitis.

The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever and chemotherapy-induced neutropenia

Aim To demonstrate whether serum Interleukin-8 (IL-8) is a relevant parameter to select hospitalised patients with chemotherapy-induced neutropenic fever with low or high probability of infection. Results 90 assessable febrile episodes in 73 patients were evaluated; 46% of the febrile episodes were microbiologically documented infection (MDI), 8% clinical documented infection (CDI), and 47% fever of unknown origin (FUO). Median IL-8 level was lower in the FUO group compared to CDI and MDI ( p < 0.0005). In 45 of 48 episodes (94%) with CDI/MDI, IL-8 level at the start was ⩾60 ng/l while in 18 of 21 episodes (86%) with IL-8 level <60 ng/l, no infectious cause was demonstrated. FUO and CDI/MDI patients with IL-8 ⩾60 ng/l and responsive on antibiotic treatment showed a decline of IL-8 levels within days in contrast to non-responding patients. Conclusions Serum IL-8 level can be a useful marker to identify hospitalised FUO patients with low probability of infection.

Bronchoalveolar lavage cytokine profile in a cohort of lung transplant recipients: A predictive role of interleukin-12 with respect to onset of bronchiolitis obliterans syndrome

Background Bronchiolitis obliterans syndrome is the main long-term complication of lung transplantation that limits survival of lung transplant patients. Its pathophysiologic mechanisms are still poorly understood but it seems to result from a chronic immunologic/inflammatory insult leading to excessive fibroproliferation. The aim of this longitudinal study of 44 lung recipients was to determine whether a number of bronchoalveolar lavage and clinical variables are associated with a higher risk of developing bronchiolitis obliterans syndrome. Methods Bronchoalveolar lavage studies involved assessment of several cytokines including: interleukin-8, monocyte chemoattractant protein-1, regulated-upon-activation normal T cell expressed and secreted (RANTES), gamma-interferon, interleukin-12, interleukin-10 and transforming growth factor-beta. Results The predictivity of bronchoalveolar lavage (BAL) features with respect to onset of bronchiolitis obliterans syndrome was assessed by the Cox regression model. Among clinical variables, bacterial and viral infections were found to significantly predict occurrence of bronchiolitis obliterans syndrome (hazard ratio [HR] for bacterial infection: 13.044, 95% confidence interval [CI] 1.34 to 126.69, p = 0.027; HR for viral infections: 4.88, 95% CI 1.004 to 22.87, p = 0.05). Among BAL variables, only IL-12 was significantly predictive of bronchiolitis obliterans syndrome (HR 0.956, 95% CI 0.901 to 1.01, p = 0.03). In addition, in a sub-group cross-sectional analysis, bronchiolitis obliterans syndrome patients were compared with clinically stable patients, and significant increases in median levels of interleukin-8 and monocyte chemoattractant protein-1 BAL fluid were detected. Conclusions These findings support the contention that interleukin-12 plays a role in the modulation of the local pro-/anti-fibrotic balance of allograft airways.

Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia.

Interleukin-8 (IL-8) is a potent neutrophil chemoattractant and activator. Pneumocystis carinii pneumonia is associated with an accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid. Thus, we hypothesized that IL-8 is involved in the pathogenesis of P. carinii pneumonia. BAL fluid and serum were prospectively collected in 76 consecutive HIV-infected patients with a primary episode of P. carinii pneumonia, as well as in 10 healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared with control subjects (p < 0.01). Nine patients died during the course of P. carinii pneumonia. Comparing survivors with nonsurvivors, the median IL-8 level in BAL fluid was 127 (0 to 3,900) versus 584 (127 to 6,100) pg/ml (p < 0.05). Furthermore, patients with levels of IL-8 in BAL fluid greater than 90 pg/ml (i.e., greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen percent required mechanical ventilation (MV). Patients requiring MV had a median IL-8 level of 396 (25 to 6,100) versus 129 (0 to 3,900) pg/ml for patients not requiring MV (p < 0.05). In conclusion: i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.

Prognostic Value of Interleukin-8 in AIDS-associated Pneumocystis carinii Pneumonia

Interleukin-8 (IL-8) is a potent neutrophil chemoattractant and activator. Pneumocystis carinii pneumonia is associated with an accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid. Thus, we hypothesized that IL-8 is involved in the pathogenesis of P. carinii pneumonia. BAL fluid and serum were prospectively collected in 76 consecutive HIV-infected patients with a primary episode of P. carinii pneumonia, as well as in 10 healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared with control subjects (p < 0.01). Nine patients died during the course of P. carinii pneumonia. Comparing survivors with nonsurvivors, the median IL-8 level in BAL fluid was 127 (0 to 3,900) versus 584 (127 to 6,100) pg/ml (p < 0.05). Furthermore, patients with levels of IL-8 in BAL fluid greater than 90 pg/ml (i.e., greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen percent required mechanical ventilation (MV). Patients requiring MV had a median IL-8 level of 396 (25 to 6,100) versus 129 (0 to 3,900) pg/ml for patients not requiring MV (p < 0.05). i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.