interleukin-8 and Neutropenia

Topics: Apoptosis; Chediak-Higashi Syndrome; Familial Mediterranean Fever; Humans; Inflammation; Interleukin-1; Interleukin-8; Leukocyte-Adhesion Deficiency Syndrome; Neutropenia; Neutrophil Activation; Neutrophils; Phagocytosis

The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3°C due to various causes.. Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection.. IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values.. High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer.

Topics: Antineoplastic Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Fibrin Fibrinogen Degradation Products; Humans; Infections; Interleukin-8; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Male; Neoplasms; Neutropenia; Osteoprotegerin; Prospective Studies; Protein Precursors

Docetaxel (DTX) and zoledronic acid (ZOL) are effective in patients with hormone resistant prostate cancer (HRPC) with bone metastases. A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different sequences was conducted in HRPC.. The maximum tolerated dose was not achieved with sequence A. Two patients at third level of sequence B developed dose limiting toxicity. A disease control was obtained in six out of nine patients treated with sequence A, where a decrease of biological markers and PSA were also observed. No evidence of anti-tumor activity was observed in patients treated with sequence B.. Twenty-two patients enrolled into the study (median age: 73 years; range: 43-80) received one of three escalated doses of DTX (30, 40 and 50 mg/m(2)) in combination with a fixed dose of ZOL (2 mg), both administered every 14 days in two different sequences: DTX at the day 1 followed by ZOL at the day 2 (sequence A) or the reverse (sequence B). Patients were evaluated for adverse events and serum IL-8, MMP-2 and MMP-9 were evaluated prior and after therapy with the two sequences of administration of DTX and ZOL.. The bi-weekly combination of DTX (50 mg/m(2)) followed by ZOL was feasible and show promising anti-tumor activity.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Diphosphonates; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Fever; Humans; Imidazoles; Infusions, Intravenous; Interleukin-8; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Neutropenia; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Treatment Outcome; Zoledronic Acid

Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can have important implications in terms of management. We aimed to identify a serum marker that may help to stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first evaluation. Thus, C-reactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-alpha (MCP-1-alpha) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer patients.. Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed clinical data of 85 fever episodes occurring in 76 patients with hematologic malignancies, presenting to the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month period.. Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable fever (group I, n=26) and another group with either blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection (group II, n=59). Clinically, local sites of infection were encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and MCP-1 levels were significantly lower in group I versus group II (P value <0.001). There were overlaps of values between groups. CRP > or =90 mg/L was significantly associated with chemotherapy-related neutropenia and fever owing to bacteremia (P=0.038). The sensitivity, specificity, negative and positive predictive values of CRP, MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%), respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as 78% of group II had elevated 2 or 3 markers versus 16% of the group with no evident infection.. Low levels of CRP, MCP-1, and IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment of febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; C-Reactive Protein; Chemokine CCL2; Child; Child, Preschool; Female; Fever; Hematologic Neoplasms; Humans; Infant; Interleukin-8; Leukemia; Male; Neutropenia; Predictive Value of Tests; Prognosis; Prospective Studies; Reference Values; Risk Factors; Treatment Outcome

Children with cancer often develop febrile illnesses after cytotoxic chemotherapy. Determining which children have serious bacterial infections in this vulnerable period would be valuable. We evaluated the ability of a rapid and sensitive assay for the concentration of calcitonin precursors (CTpr) as a sensitive diagnostic marker for bacterial sepsis in febrile, neutropenic children and determined the utility of measuring cytokines to improve the predictive value of this approach.. Prospective cohort study.. Academic children's hospital.. Fifty-six children (aged 5 months to 17 yrs) with a known malignancy who presented with fever and neutropenia.. Serial blood samples were obtained (admission, 24 hrs, and 48 hrs), and concentrations of CTpr, interleukin-6, and interleukin-8 were determined. Demographic and laboratory data from the patients were collected from the medical record.. Sixteen (29%) of the children met the criteria for bacterial sepsis. Plasma levels of CTpr and interleukin-8, but not interleukin-6, were increased at all time points in children with sepsis compared with those without sepsis. CTpr at 24 and 48 hrs after admission were reliable markers for sepsis (area under the curve = 0.92 and 0.908, respectively). Logistic regression using CTpr at 24 hrs in addition to interleukin-8 at 48 hrs produced the best-fit models associated with sepsis. Using cutoff values of CTpr >500 pg/mL and interleukin-8 >20 pg/mL produced a screening test for sepsis with 94% sensitivity and 90% specificity.. Our data show the utility of a rapid and sensitive assay for CTpr combined with interleukin-8 as a highly sensitive and specific diagnostic marker of bacterial sepsis in febrile, neutropenic children. The use of these markers as a clinical tool may allow for better prognostication for clinicians and may eventually lead to more targeted therapies for this heterogeneous population.

Topics: Adolescent; Bacterial Infections; Calcitonin; Child; Child, Preschool; Female; Fever; Follow-Up Studies; Humans; Infant; Interleukin-6; Interleukin-8; Luminescent Measurements; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Topics: Adult; Aged; Bacteremia; Biomarkers; Chi-Square Distribution; E-Selectin; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Immunoenzyme Techniques; Interleukin-10; Interleukin-8; Male; Middle Aged; Neutropenia; Sensitivity and Specificity

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Topics: Calcium-Binding Proteins; Cardiopulmonary Bypass; Child; Heart Defects, Congenital; Hemofiltration; Humans; Interleukin-8; Intraoperative Care; Leukocyte Count; Leukocyte L1 Antigen Complex; Leukocytosis; Lymphocyte Count; Neural Cell Adhesion Molecules; Neutropenia; Neutrophils; Prospective Studies; Time Factors

Topics: Adolescent; Biomarkers; Child; Female; Fever; Humans; Infant; Inflammation; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Prospective Studies; Sepsis

In this analysis, the levels of CRP and IL-8 were employed as a guide for designing the duration of antibiotics administration in the condition of febrile neutropenia. The importance of laboratory biomarkers is in the early diagnosis of critical illness and adjustment of further management. IL-8 is a useful biomarker for the early identification of critically ill patients, compared to CRP in FN.

Topics: C-Reactive Protein; Child; Fever; Hematopoietic Stem Cell Transplantation; Humans; Interleukin-8; Neutropenia; Risk Assessment; Sensitivity and Specificity

Whether presepsin (soluble CD14-subtype) is better than other markers including procalcitonin (PCT), has not been adequately investigated in febrile neutropenia (FN).. We prospectively examined the utility of presepsin in FN in Cohort 1 (C1) and 2 (C2), between November 2010 and February 2012, and between November 2013 and January 2014, respectively. The purpose of this study was to investigate 1) the relative value of serum presepsin over serum PCT in C1, and 2) the relative value of plasma presepsin as compared with serum PCT, C-reactive protein, interleukin-6 and interleukin-8 with frequent, repeated sampling in C2.. Seventy-nine FN episodes (C1, 75; C2, 4) were evaluable. In C1, when compared with control values, presepsin was significantly higher at onset of FN (P = 0.004), while PCT was not significantly higher (P = 0.54). The median value of serum presepsin within 72 h of onset of FN in subjects with fever of unknown origin, local infection, bacteremia and septic shock was 680 (reference 314) pg/ml, 763, 782 and 1359, respectively. In C2, the mean levels of plasma presepsin from onset of FN to 72 h were classified as negative in the two patients with no suspected site of infection, and those of the remaining two patients with clinically probable infections were positive (175, 131, 346 and 329 pg/ml, respectively). In contrast, the other markers did not discriminate between this two groups.. In FN, presepsin may be an earlier and more sensitive indicator of bacterial infection than PCT.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Cohort Studies; Female; Hematologic Diseases; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Middle Aged; Neutropenia; Peptide Fragments; Prospective Studies; Young Adult

Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.. We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia.. Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups.. Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.

Topics: Acute Kidney Injury; Adult; Aged; Angiopoietin-2; APACHE; Biomarkers; Chi-Square Distribution; Cohort Studies; Critical Illness; Female; Granulocyte Colony-Stimulating Factor; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Neutropenia; Pennsylvania; Prospective Studies; Receptors, Interleukin-1; Respiratory Distress Syndrome; Sepsis

Granulocyte colony stimulating factor (G-CSF) restores neutrophil count in patients with chemotherapy-induced neutropenia. G-CSF can also induce production of epithelial neutrophil activating protein-78 (ENA-78) and interleukin-8 (IL-8), chemotactic factors from neutrophils in vitro. This study was purposed to investigate whether this effect is also observed in vivo. 10 lymphoma patients were selected who received chemotherapy and G-CSF (nartograstim) administration. Blood was obtained before chemotherapy [Time Point 1 (TP1)], at neutropenic phase before G-CSF administration (TP2), and at neutrophil recovery phase after G-CSF (TP3). ENA-78 and IL-8 mRNA in neutrophils were quantified by real-time PCR. Phagocytosis and reactive oxygen species (ROS) generation were examined by flow cytometry. The results showed that ENA-78 and IL-8 mRNA expression at TP2 increased in 5 and 8 patients, respectively. The ENA-78 mRNA expression at TP3 was increased in 3 and decreased in 6 patients, and IL-8 mRNA expression at TP3 decreased in 7 patients. G-CSF did not affect phagocytosis and normalized ROS generation in all of the patient. It is concluded that increase of ENA-78 and IL-8 expression in neutrophils is common in chemotherapy-induced neutropenic patients. G-CSF administration does not significantly increase ENA-78 and IL-8 expression.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemokine CXCL5; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; Lymphoma; Male; Middle Aged; Neutropenia; Neutrophils; RNA, Messenger

Despite a low bacteremia rate, pediatric oncology patients are frequently admitted for febrile neutropenia. A pediatric risk prediction model with high sensitivity to identify patients at low risk for bacteremia is not available. We performed a single-institution prospective cohort study of pediatric oncology patients with febrile neutropenia to create a risk prediction model using clinical factors, respiratory viral infection, and cytokine expression.. Pediatric oncology patients with febrile neutropenia were enrolled between March 30, 2010 and April 1, 2011 and managed per institutional protocol. Blood samples for C-reactive protein and cytokine expression and nasopharyngeal swabs for respiratory viral testing were obtained. Medical records were reviewed for clinical data. Statistical analysis utilized mixed multiple logistic regression modeling.. During the 12-month period, 195 febrile neutropenia episodes were enrolled. There were 24 (12%) episodes of bacteremia. Univariate analysis revealed several factors predictive for bacteremia, and interleukin (IL)-8 was the most predictive variable in the multivariate stepwise logistic regression. Low serum IL-8 predicted patients at low risk for bacteremia with a sensitivity of 0.9 and negative predictive value of 0.98.. IL-8 is a highly sensitive predictor for patients at low risk for bacteremia. IL-8 should be utilized in a multi-institution prospective trial to assign risk stratification to pediatric patients admitted with febrile neutropenia.

Topics: Adolescent; Adult; Bacteremia; Bacteria; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Infant; Interleukin-8; Male; Neoplasms; Neutropenia; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Young Adult

The soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is a useful marker of infection in patients with sepsis, but has not been adequately evaluated in patients with chemotherapy-associated febrile neutropenia (FN). The value of sTREM-1 in this setting has been tested in a retrospective, pilot study using stored serum from 48 cancer patients with documented FN. On presentation, patients were categorized according to the Talcott risk-index clinical score. Circulating soluble sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an immunoluminescence-based assay and Bio-Plex® suspension bead array system, respectively. Circulating concentrations of both sTREM-1 and PCT were significantly (P < 0.05) elevated in patients at high risk for complications or death, as predicted by the Talcott score and were significantly lower in patients who responded to empiric antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications in patients with FN. These observations, albeit from a pilot study, demonstrate that sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to predict their clinical course, either together with, or as an alternative to PCT.

Topics: Anti-Infective Agents; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Interleukin-6; Interleukin-8; Male; Membrane Glycoproteins; Middle Aged; Neutropenia; Pilot Projects; Protein Precursors; Receptors, Immunologic; Retrospective Studies; ROC Curve; Triggering Receptor Expressed on Myeloid Cells-1

Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia.. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer.. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis.. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.

Topics: Adolescent; Bacteremia; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Female; Fever; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Sepsis

Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome.. Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome.. Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α.. Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.

Topics: Adolescent; Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Intensive Care Units; Interleukin-10; Interleukin-3; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Pilot Projects; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; ROC Curve; Tumor Necrosis Factor-alpha; Young Adult

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis.. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26).. At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels.. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8.

Topics: Adolescent; Antineoplastic Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Fever; Gastrointestinal Tract; Humans; Interleukin-8; Male; Membrane Glycoproteins; Mucositis; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Triggering Receptor Expressed on Myeloid Cells-1

Primary autoimmune neutropenia (AIN) is more common in newborns, and usually benign or self-limiting, so most cases require no specific therapy. In adults, however, for little tendency toward spontaneous remission, they require certain treatments and careful managements. Here we report a successful management of primary AIN patient by estimating the granulopoiesis according to CRP levels without administration of G-CSF or increase of prednisolone when peripheral neutrophil counts dropped down. Transient elevation of CRP associated with severe drop down in neutrophil count, and subsequent dramatic neutrophil increase was occasionally observed during the follow up with minimal dose of prednisolone. Coexistence of decreased neutrophil counts and elevated CRP levels was accompanied by increase of serum levels of IL-6 and IL-8. Although this is the report of only one patient, these elevated CRP levels combined with severe drop down and subsequently spontaneous rapid recovery in neutrophil count, were repetitively observed, suggesting the preceding CRP elevation before neutrophil recovery. We propose the important part of CRP as a predictor of granulopoiesis in patients with neutropenia.

Topics: Autoimmune Diseases; Biomarkers; C-Reactive Protein; Cell Count; Female; Humans; Interleukin-6; Interleukin-8; Middle Aged; Neutropenia; Neutrophils; Prognosis

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Critical Care; Critical Illness; Early Diagnosis; Female; Fever; Humans; Intensive Care Units; Interleukin-8; Male; Membrane Glycoproteins; Neutropenia; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Survival Analysis; Triggering Receptor Expressed on Myeloid Cells-1

We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.

Topics: Animals; Asialoglycoprotein Receptor; Blood Platelets; Child; Female; Granulocytes; Humans; Interleukin-8; Liver; Mice; Mutation; N-Acetylneuraminic Acid; Neutropenia; Nucleotide Transport Proteins; Oligosaccharides; Phenotype; Protein Binding; Selectins; Sialyl Lewis X Antigen; Thrombocytopenia

This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia.. We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-α), two soluble TNF-α receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2-3 ml of plasma was obtained from each blood sample and stored at -80 °C.. The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1.. Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cause of Death; Chemokine CCL11; Chemokine CCL2; Chemokine CCL3; Epidemiologic Methods; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutropenia; Prospective Studies; Protein Precursors; Receptors, Tumor Necrosis Factor, Type I; Time Factors; Tumor Necrosis Factor-alpha

The aim of this study was to assess the value of procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1b, IL-8, and soluble TNF receptor II (sTNFRII) in early and rapid diagnosis of infection in neutropenic children with acute lymphoblastic leukemia (ALL) and to distinguish bacterial from viral infections.. The study included five groups (A, B, C, D, and E) of children with ALL undergoing intensive chemotherapy. Groups A and B consisted of neutropenic children with bacterial and viral infection, respectively. Groups C and D consisted of nonneutropenic children with bacterial and viral infection, respectively. Group E consisted of children without neutropenia and without fever.. In all groups, blood samples were collected upon admission and then for 7 days on a daily basis. Levels of CRP, PCT, TNF-a, IL-1b, IL-8, and sTNFRII were determined in all blood samples.. We found a highly significant difference in PCT levels between bacterial and nonbacterial episodes. Sensitivity and specificity of PCT were 94 and 96.5%, respectively.. Serial measurement of PCT levels on a daily basis seems to be helpful for early prediction of severe bacterial infections, monitoring febrile episodes regarding response to antibiotic therapy, and early detection of complications in the infectious process.

Topics: Adolescent; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Fever; Humans; Infant; Interleukin-1beta; Interleukin-8; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Precursors; Receptors, Tumor Necrosis Factor, Type II; ROC Curve; Tumor Necrosis Factor-alpha

Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Candidiasis; Cytokines; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutropenia; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha

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.. 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 > or =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 > or =60 ng/l and responsive on antibiotic treatment showed a decline of IL-8 levels within days in contrast to non-responding patients.. Serum IL-8 level can be a useful marker to identify hospitalised FUO patients with low probability of infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Biomarkers; C-Reactive Protein; Female; Fever of Unknown Origin; Hospitalization; Humans; Interleukin-8; Male; Middle Aged; Neutropenia; Opportunistic Infections; Prospective Studies; Sensitivity and Specificity; Young Adult

Infectious complications in neutropenic patients are a major cause of morbidity and mortality. Clinical signs are unspecific and fever can be attributed to other causes. Inflammatory biomarkers have emerged as potentially useful in diagnosis of bacterial and fungal infection. Levels of several biomarkers were measured in patients with hematological malignancy at diagnosis and at the beginning of neutropenia due to cytostatic treatment or after hematopoietic stem cell transplantation, and daily until 6 days after presenting fever. Procalcitonin (PCT) and neopterin levels were not elevated at diagnosis or at the beginning of neutropenia. C-reactive protein (CRP) was moderately elevated. PCT levels were significantly higher in patients with Gram-negative bacteremia at 24-48 h after the onset of fever. Patients with probable fungal infection presented elevated PCT values when fever persisted for more than 4-5 days. CRP was more sensitive to predict bacteremia (both Gram-positive and Gram-negative) but the specificity was low. Neither neopterin, IL-6 nor IL-8 presented significant differences according to the origin or etiology of fever. Since it showed a high negative predictive value of Gram-negative bacteremia, clinical prediction rules that attempt to predict a high risk of severe infection might be improved by including measurement of PCT.

Topics: Adult; Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Hematologic Neoplasms; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Mycoses; Neopterin; Neutropenia; Opportunistic Infections; Predictive Value of Tests; Protein Precursors

Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia.. A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics.. The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%).. These findings may have clinical implications for risk-based antimicrobial treatment strategies.

Topics: Adolescent; Adult; Anti-Bacterial Agents; C-Reactive Protein; Ceftazidime; Child; Child, Preschool; Female; Fever; Germany; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Prospective Studies; Risk Factors; Sepsis

Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident.. Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis.. A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08).. Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Topics: Adolescent; Age Factors; Biomarkers; Blood Glucose; Blood Urea Nitrogen; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Chile; Female; Fever of Unknown Origin; Hospitalization; Humans; Interleukin-8; L-Lactate Dehydrogenase; Logistic Models; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Sepsis

The primary objective of the study was to compare the predictive potential of procalcitonin (PCT), C-reactive protein (CRP), serum amyloid A (SAA), and interleukin (IL)-1beta, IL-6, IL-8, and IL-10, with that of the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score in cancer patients on presentation with chemotherapy-induced febrile neutropenia (FN). Seventy-eight consecutive FN episodes in 63 patients were included, and MASCC scores, as well as concentrations of CRP, SAA, PCT, and IL-1beta, IL-6, IL-8 and IL-10, and haematological parameters were determined on presentation, 72 h later and at outcome. Multivariate analysis of data revealed the MASCC score, but none of the laboratory parameters, to be an accurate, independent variable (P < 0.0001) for prediction of resolution with or without complications and death. Of the various laboratory parameters, PCT had the strongest association with the MASCC score (r = -0.51; P < 0.0001). In cancer patients who present with FN, the MASCC risk-index score is a useful predictor of outcome, while measurement of PCT, CRP, SAA, or IL-1beta, IL-6, IL-8 and IL-10, is of limited value.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Fever; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Logistic Models; Male; Middle Aged; Neoplasms; Neutropenia; Predictive Value of Tests; Prognosis; Protein Precursors; Serum Amyloid A Protein; Treatment Outcome

Topics: Bacterial Infections; Biomarkers; Child; Cytokines; Humans; Interleukin-5; Interleukin-8; Neoplasms; Neutropenia; Opportunistic Infections

To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model.. Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol.. Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of 471 (US $572) for every potentially low-risk patient.. This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Feasibility Studies; Female; Fever; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Middle Aged; Neoplasms; Neutropenia; Patient Discharge; Predictive Value of Tests; Prospective Studies; Risk Assessment

Previous studies have shown that interleukin-8 serum levels in febrile neutropenic patients are significantly higher in patients with gram-negative bacteremia than in patients with other causes of fever and may indicate unfavorable outcomes. We assessed the value of interleukin-8 serum levels at fever onset to predict clinical complications in order to confirm these earlier findings.. In a prospective observational study of adult patients receiving cancer chemotherapy, serum samples obtained at the onset of 147 febrile neutropenic episodes were measured by an immunoluminescence assay.. Complicated courses of fever including severe sepsis or septic shock, respiratory insufficiency or death were observed in 13 episodes (9%); in six episodes complications had developed within 1 week after fever onset and five of them were associated with bloodstream infections. At an interleukin-8 cutoff level of 1,000 pg/ml, these early complications were predicted with a sensitivity of 83%, a specificity of 97%, a positive predictive value of 50%, and a negative predictive value of 99%, respectively.. Interleukin-8 levels at fever onset may be used for the prediction of early medical complications associated with bacteremia and can help identify patients who might benefit from intensive care admission.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bacteremia; Fever; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Middle Aged; Neutropenia; Predictive Value of Tests; Prognosis; Prospective Studies

To compare serum levels of interleukin-6, interleukin-8 and interleukin-10 in bacteremic and non-bacteremic episodes of febrile neutropenia in children with malignant diseases, and determine their changes and correlation with C-reactive protein (CRP).. Between January 2003 and June 2004, we examined 41 episodes of febrile neutropenia in 24 children with malignant diseases who were receiving polychemotherapy. C-reactive protein was measured at the onset of febrile episodes and on days 3 and 5 from beginning of therapy. The soluble interleukins-6, -8, and -10 were determined in the serum using enzyme bound immunosorbent analysis at the onset of fever and at 24 and 72 hours after initiation of an empiric antibiotic therapy.. The CRP baseline levels differentiated the patients with unexplained fever from those with local infection but did not differentiate them from those with bacteremia. Interleukin-8 at 24 hours differentiated bacteremic from non-bacteremic episodes (P < 0.05) and at a cut-off value of 130 pg/ml it had a sensitivity of 72% and a specificity of 84% to differentiate bacteremia. Interleukin-10 at 24 hours yielded higher values in Gram (-) bacteremia in comparison with the non-bacteremic episodes (P < 0.001) and Gram (+) bacteremia (P < 0.05). Interleukin-6 at 24 hours had significantly higher values in febrile episodes of more than 3 days duration (P < 0.05).. Interleukin-8 could differentiate in the first 24 hours bacteremic from non-bacteremic episodes in febrile neutropenia, while interleukin-10 is perhaps a more accurate marker for Gram (-) bacteremia.

Topics: Adolescent; Adult; Analysis of Variance; Bacteremia; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Statistics, Nonparametric

The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1beta, IL8, and TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.

Topics: Bacteremia; Cells, Cultured; Cytokines; Humans; Inflammation; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Neutropenia; Sepsis; Tumor Necrosis Factor-alpha; Viridans Streptococci

Enterocolitis in oncology patients remains an important complication, but there is a lack of insight into its likely severity from microbial, pathological and inflammatory aspects. Paediatric oncology patients admitted with neutropenic fever, who developed abdominal pain and diarrhoea, were monitored by the takers of rectal biopsies, cultures, and inflammatory marker measurements. Twenty-five patients were included (mean age 7.1 years). 8 patients (32%) needed intensive care treatment, 3 (12%) patients died. Gram-positive bacteraemia was diagnosed in 4 patients (16%). Most patients had negative blood and stool cultures. Predictors of a severe clinical course of the enterocolitis were an increased serum interleukin-8 (IL-8) (>1000 pg/ml) level and an increased serum C-reactive protein level (CRP) (>150 mg/l) level, both measured on the first day of clinical illness. Relative risks (RR) for admission to an Intensive Care Unit (ICU) were 11.3 (95% Confidence Interval (CI) 1.6-77.9) for elevated IL-8 levels and 6.4 (95% (CI) 0.92-45.1) for increased CRP levels. Rectal biopsies and pathology could not predict outcome (P=0.22). IL-8 analysis at the onset of enterocolitis symptoms can identify high-risk patients, which might be used clinically to design future intervention trials.

Topics: Abdominal Pain; Biopsy; C-Reactive Protein; Child; Diarrhea; Enterocolitis; Female; Fever; Humans; Interleukin-8; Male; Neoplasms; Neutropenia; Physical Examination; Prognosis; Prospective Studies; Rectum

N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit models of ear edema and neutropenia.

Topics: Animals; Anti-Inflammatory Agents; Binding, Competitive; Calcium; Chemokine CXCL1; Chemokines; Chemotactic Factors; Chemotaxis; CHO Cells; Cricetinae; Humans; Hypersensitivity, Delayed; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Interleukin-8; Neutropenia; Neutrophils; Phenylurea Compounds; Rabbits; Radioligand Assay; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Structure-Activity Relationship

Topics: Biomarkers; Child; Fever; Genotype; Humans; Infections; Interleukin-6; Interleukin-8; Neoplasms; Neutropenia; Point Mutation; Promoter Regions, Genetic

The aim of the study was to evaluate the ability of procalcitonin, C-reactive protein, serum amyloid A, interleukin-6 and interleukin-8 to predict bacteraemia during the 2 first d of fever in neutropenic patients. A total of 94 febrile neutropenic episodes in 60 patients were studied. Plasma samples were analysed at 10-h intervals from the onset of fever. Clinical events were categorized into 4 groups: 1) bacteraemia caused by other agents than coagulase-negative staphylococci (non-CNS bacteraemia) (n = 21), 2) coagulase-negative staphylococci bacteraemia (n = 15), 3) microbiologically or clinically documented infection without bacteraemia (n = 26) and 4) fever of unknown origin (n = 32). In non-CNS bacteraemia all markers, except for serum amyloid A, showed significantly higher levels compared to patients with fever of unknown origin (p < 0.05). For non-CNS bacteraemia the highest negative predictive value was found for procalcitonin (94%), followed by interleukin-6 (89%), C-reactive protein (88%) and interleukin-8 (87%). Procalcitonin, with a cut-off level of 1.4 ng/ml during 10-20 h after fever onset, showed the highest positive predictive value (67%) for a non-CNS bacteraemia. In conclusion, the value of the analysed markers to predict a non-CNS bacteraemia in neutropenic patients was limited due to low sensitivity and positive predictive value. However, procalcitonin, interleukin-6, C-reactive protein, and interleukin-8 could give useful information for the clinician in excluding a non-CNS bacteraemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amyloid; Analysis of Variance; Antineoplastic Agents; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Fever; Hematologic Neoplasms; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutropenia; Probability; Prognosis; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

We studied the role of interleukin (IL)-8 during engraftment after hematopoietic stem cell transplantation. In 40 consecutive patients undergoing either allogeneic marrow (n=32) or autologous peripheral blood stem cell transplantation (n=8), IL-8 plasma levels were serially determined. Median IL-8 concentrations peaked during the neutropenic phase and, subsequently, subsided to pretransplant levels in patients achieving engraftment. In all patients, we observed an inverse correlation of IL-8 with leukocytes (P<0.0001) and a direct correlation of IL-8 with the extent of neutropenia (P<0.0001). Four patients who developed graft failure showed sustained median IL-8 concentrations of >300 pg/mL together with persistent neutropenia. This marked elevation of IL-8 was statistically significant as early as day 11 after transplantation, at a time when no other evidence alluded to imminent graft failure. Our data suggest that IL-8 may play an important role during engraftment after hematopoietic stem cell transplantation.

Topics: Humans; Interleukin-8; Neutropenia; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous

This study was conducted on thirty-seven neonates and healthy neonates (sixteen full term and fourteen preterm). The study aimed at revealing the role played by the NK cells in neonatal sepsis and evaluating the sensitivity of NK cell number and cytotoxicity as diagnostic markers in infants with suspected early neonatal sepsis compared with the circulating cytokine IL-8 and CRP levels. All samples of peripheral blood lymphocytes were subjected to determination of CD16 and CD56 positive cells using flow cytometry and NK cytotoxicity using the standard 4h 51Cr release assay. Sera were separated to measure IL-8 using ELISA. Determination of CRP, using turbdimetric assay, as well as blood cultures were done for patient's group only. Out of the 37 cases of suspected early neonatal sepsis, 16 were given final diagnosis of sepsis. Seven infants (43.8%) in the sepsis group had culture-proven diagnosis, one of which had meningitis. The median CRP value was significantly higher in sepsis group (88 mg/L; range: 17-159 mg/L) compared with that in non-septic group (15.4 mg/L; range: 7.6-23.2 mg/L, p < 0.001) only 12-60 h after admission. On the other hand, newborns in the sepsis group had significantly higher serum levels of IL-8 (median 310 pg/mL; range: 37-583 pg/ml) at study entry than that in the non septic group (median 63 pg/mL; range: 32-94 pg/ml, P < 0.001). On admission, the NK activity, rather than the number of CD16 and CD56 positive cells was much affected where NK cytotoxicity was significantly lower in sepsis group (3.4 +/- 2.1%, range 0.9-7%) than that of the nonseptic group (18.3 +/- 6.7%: range 10.7- 25.3%, p < 0.01) and healthy neonates (23.8 +/- 4.7%: range 12.2-32.3%, p < 0.001). We may conclude that defective NK cell activity rather than NK cell number plays an important role in susceptibility to early onset neonatal sepsis. Evaluation of NK cytotoxicity as a marker in early diagnosis of neonatal sepsis reveals that the sensitivity, specificity and predictive values of reduced NK cytotoxicity (10% killing) was higher than both of CRP and IL-8, either individually or in combination. Additionally, reduced NK cytotoxicity showed high correlation with the severity and outcome of neonatal sepsis. Our data raise the possibility that the addition of NK cell activity to the standard work-up of critically ill patients with suspected sepsis could increase diagnostic certainty and generate an improved patient management.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; CD56 Antigen; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Female; Flow Cytometry; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Killer Cells, Natural; Leukocyte Count; Male; Neutropenia; Predictive Value of Tests; Receptors, IgG; Sensitivity and Specificity; Sepsis

Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE.

Topics: Apoptosis; Autoantibodies; Autoantigens; Base Sequence; Chromatography, Affinity; DNA, Complementary; Gene Expression; Humans; Interleukin-8; Jurkat Cells; Lupus Erythematosus, Systemic; Molecular Sequence Data; Neutropenia; Neutrophils; Phagocytosis; Ribonucleoproteins; SS-B Antigen

The cytokine interleukin-8 (IL-8) binds with high affinity to the CXCR1 and CXCR2 receptors on neutrophils. In previous studies, we showed that (99m)Tc-IL-8 could rapidly and effectively delineate foci of infection and inflammation in rabbit models of intramuscular infection, colitis, and osteomyelitis. Here, the in vivo kinetics and pharmacodynamics of (99m)Tc-IL-8 are studied in detail. A derivative of hydrazinonicotinamide (HYNIC) was used as a bifunctional coupling agent to label the protein with (99m)Tc.. To address specificity of uptake of (99m)Tc-IL-8 in the abscess, uptake in turpentine-induced abscesses in neutropenic rabbits was compared with uptake in turpentine-induced abscesses in normal rabbits. The pharmacokinetics of (99m)Tc-IL-8 were studied in neutropenic rabbits and compared with those in normal rabbits. To investigate the interaction of (99m)Tc-IL-8 with blood cells in circulation in normal rabbits, the distribution of the radiolabel over circulating white and red blood cells and plasma was determined. The in vivo kinetics of (99m)Tc-IL-8 were studied by quantitative analysis of whole-body images acquired between 0 and 6 h after injection. The results of this analysis (in vivo biodistribution) were validated by ex vivo counting of radioactivity in dissected tissues.. The abscess uptake (percentage of injected dose per gram of tissue [%ID/g] +/- SEM) in immunocompetent rabbits (0.41 +/- 0.05) was 10 times higher than that in neutropenic rabbits (0.038 +/- 0.014), demonstrating specificity of the target uptake of (99m)Tc-IL-8. Abscess-to-muscle ratios +/- SEM were also 10 times higher (110 +/- 10 vs. 10 +/- 5). Lung and spleen uptake in normal rabbits was 3 times higher than that in neutropenic rabbits. The blood clearance of the radiolabel in neutropenic rabbits was similar to that in normal rabbits. In circulation, most of (99m)Tc-IL-8 (70%) was found in the plasma fraction. Less than one third was associated with red blood cells, and only a very low percentage (<2.5%) was associated with white blood cells. Image analysis revealed a gradually increasing abscess uptake over time up to >15%ID, which was confirmed by ex vivo gamma-counting of the infected muscle. The highest increase in uptake in the abscess was observed after 2 h following injection, when most of (99m)Tc-IL-8 was cleared from the blood, suggesting specific neutrophil-mediated accumulation of (99m)Tc-IL-8 in the abscess. Furthermore, region-of-interest analysis revealed that gradual accumulation of (99m)Tc-IL-8 in the abscess was accompanied by a simultaneous clearance of activity from the lungs, suggesting that neutrophil-associated (99m)Tc-IL-8 that was initially trapped in the lungs migrates to the abscess at later time points, favoring neutrophil-bound transportation from the lungs to the abscess.. Substantial support is given for the hypothesis that (99m)Tc-IL-8 localizes in the abscess, mainly bound to peripheral neutrophils. Accumulation in the abscess is a highly specific, neutrophil-driven process. As assessed by in vivo and ex vivo analysis, the total fraction that accumulates in the inflamed tissue is extremely high (up to >15 %ID) compared with that of other agents used for imaging infection and inflammation.

Topics: Abscess; Animals; Erythrocytes; Female; Infections; Inflammation; Interleukin-8; Kinetics; Leukocytes; Neutropenia; Neutrophils; Organ Specificity; Organotechnetium Compounds; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution; Turpentine; Whole-Body Counting

Chemokines are a group of structurally related peptides that promote the directed migration of leukocytes in tissue. Mechanisms controlling the retention of chemokines in tissue are not well understood. In this study we present evidence that two different mechanisms control the persistence of the CXC chemokine, IL-8, in lungs and skin. (125)I-labeled IL-8 was injected into the airspaces of the lungs and the dermis of the skin and the amount of (125)I-labeled IL-8 that remained at specified times was measured by scintillation counting. The (125)I-labeled IL-8 was cleared much more rapidly from skin than lungs, as only 2% of the (125)I-labeled IL-8 remained in skin at 4 h whereas 50% of the (125)I-labeled IL-8 remained in lungs at 4 h. Studies in neutropenic rabbits showed that neutrophils shortened the retention of (125)I-labeled IL-8 in skin but not lungs. A monomeric form of IL-8, N-methyl-leucine 25 IL-8, was not retained as long in lungs as recombinant human IL-8, indicating that dimerization of IL-8 is a mechanism that increases the local concentration and prolongs the retention of (125)I-labeled IL-8 in lungs. These observations show that the mechanisms that control the retention of IL-8 in tissue include neutrophil migration and dimerization, and that the importance of these varies in different tissues.

Topics: Animals; Female; Injections, Intradermal; Injections, Intravenous; Interleukin-8; Intubation, Intratracheal; Iodine Radioisotopes; Lung; Neutropenia; Neutrophil Infiltration; Organ Specificity; Rabbits; Skin; Vinblastine

The CXC chemokine interleukin-8 (IL-8/CXCL8) induces rapid mobilization of hematopoietic progenitor cells (HPCs). Previously we showed that mobilization could be prevented completely in mice by pretreatment with neutralizing antibodies against the beta2-integrin LFA-1 (CD11a). In addition, murine HPCs do not express LFA-1, indicating that mobilization requires a population of accessory cells. Here we show that polymorphonuclear cells (PMNs) serve as key regulators in IL-8-induced HPC mobilization. The role of PMNs was studied in mice rendered neutropenic by administration of a single injection of antineutrophil antibodies. Absolute neutropenia was observed up to 3-5 days with a rebound neutrophilia at day 7. The IL-8-induced mobilizing capacity was reduced significantly during the neutropenic phase, reappeared with recurrence of the PMNs, and was increased proportionally during the neutrophilic phase. In neutropenic mice, the IL-8-induced mobilizing capacity was restored by the infusion of purified PMNs but not by infusion of mononuclear cells. Circulating metalloproteinase gelatinase B (MMP-9) levels were detectable only in neutropenic animals treated with PMNs in combination with IL-8, showing that in vivo activated PMNs are required for the restoration of mobilization. However, IL-8-induced mobilization was not affected in MMP-9-deficient mice, indicating that MMP-9 is not indispensable for mobilization. These data demonstrate that IL-8-induced mobilization of HPCs requires the in vivo activation of circulating PMNs.

Topics: Animals; Antibodies, Monoclonal; Cells, Cultured; Dose-Response Relationship, Drug; Flow Cytometry; Hematopoietic Stem Cells; Interleukin-8; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Neutropenia; Neutrophils; Recombinant Proteins; Time Factors

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Gentamicins; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Predictive Value of Tests; Prospective Studies

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Fever; Humans; Interleukin-8; Neoplasms; Neutropenia; Protein Precursors

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, the soluble IL-2 receptor (sIL-2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy-induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram-negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy-induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut-off level 0.5 microg/l) was a more sensitive and more specific parameter in the diagnosis of high-risk (gram-negative bacteraemia) and low-risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.

Topics: Adolescent; Adult; Antigens, CD; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child; Child, Preschool; Cytokines; Female; Fever; Fever of Unknown Origin; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Protein Precursors; Receptors, Interleukin-2; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Retrospective Studies; Sensitivity and Specificity

We assessed the predictive value of procalcitonin (PCT) serum levels in neutropenic patients with fever and various types of infection, using a prospective 3 times weekly blood sampling protocol during 103 patient episodes. Compared with pre-fever levels, median PCT levels increased after fever onset from 0.16 ng/ml (day -1) to 0.34 ng/ml (day +1). In samples obtained within 32 h after fever onset, PCT levels differed significantly between (clinically or microbiologically) documented infection and unexplained fever (median 0.51 vs. 0.26 ng/ml), between bacteraemia and non-bacteraemic infection (median 0.8 vs. 0.27 ng/ml) and between Gram-negative bacteraemia and all other episodes (median 1.28 vs. 0.31 ng/ml). Receiver-operating-characteristic (ROC) curves indicated that the discriminatory power of PCT was best for predicting bacteraemia vs. non-bacteraemic infection (sensitivity 73%; specificity 86%; area under the ROC curve 0.795; cut-off value 0.5 ng/ml). Compared with interleukin-8 (IL-8) serum levels, test characteristics were similar in the prediction of bacteraemia vs. non-bacteraemic infection and in the prediction of documented infection vs. unexplained fever, while IL-8 was better than PCT in the prediction of Gram-negative bacteraemia (area under the ROC curve 0.965 vs. 0.758).

Topics: Adolescent; Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Middle Aged; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity

Circulating levels of interleukin (IL)-6, IL-8, soluble Fc gamma receptor type III (sFc gammaRIII), mannose-binding protein (MBP), and C-reactive protein (CrP) were assessed among febrile children with cancer and neutropenia. Levels of IL-6, IL-8, sFc gammaRIII, MBP, and CrP were measured in serum from 56 pediatric cancer patients at the time of admission for 121 episodes of febrile neutropenia (88 febrile episodes without identifiable source, 5 clinically documented infections, 20 episodes of bacteremia due to gram-positive and 5 due to gram-negative organisms, and 3 fungal infections). IL-6 and IL-8 levels were higher in patients with either bacteremia due to gram-negative organisms or fungal infections than in patients with febrile episodes without an identifiable source (P < .00001 for each). IL-6 and IL-8 levels were higher in children with bacteremia due to gram-negative organisms than in those with bacteremia due to gram-positive organisms (P = .0011 and P = .0003, respectively). The measured levels of CrP, MBP, and sFc gammaRIII were not useful for identifying the type of infection. These preliminary results show the potential usefulness of IL-6 and IL-8 as early indicators for life-threatening infections in febrile cancer patients with neutropenia.

Topics: Adolescent; Adult; Bacteremia; C-Reactive Protein; Carrier Proteins; Child; Collectins; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Receptors, IgG; Retrospective Studies; Solubility

The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. In this study plasma interleukin-8 (IL-8) and interleukin-6 (IL-6) levels measured at start of fever (n = 72) could define a low-risk group of febrile patients with neutropenia due to chemotherapy. For this purpose we collected and analysed data on 72 fever episodes from 53 patients with chemotherapy-related neutropenia, aged between 1 and 66 years. Of the 72 episodes, 18 were classified as bacteraemia and/or clinical sepsis (sepsis group). The IL-6 and IL-8 plasma concentration were significantly increased in patients with chemotherapy-related neutropenia and fever due to bacteraemia versus fever of non-bacterial origin (P = 0.043 and P = 0.022 respectively). Logistic regression analysis, with sepsis as the outcome variable, revealed significant effects of age combined with either IL-6 or IL-8. Sepsis occurrence was lowest for patients <16 years and highest in patients between 16 and 50 years, and was higher in patients with increased IL-6 (P = 0.032) or IL-8 (P = 0.049). No significant effect of leucocyte count, C-reactive protein, sex or underlying malignancy at presentation was detected. The plasma IL-6 and IL-8 levels were fairly strongly correlated (Pearson r = 0.62). Using a cut-off value with 100% sensitivity, both IL-8 and IL-6 could define a low-risk group of neutropenic patients of 28% (CI 15-40%) at the start of the febrile period. Intervention studies are warranted to confirm this result and to investigate whether an early discharge based on IL-8 or IL-6 measurement is safe, increases the quality of life, and results in cost savings.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; C-Reactive Protein; Child; Child, Preschool; Fever; Humans; Infant; Interleukin-6; Interleukin-8; Leukocyte Count; Middle Aged; Neoplasms; Neutropenia; Risk Factors; Sensitivity and Specificity; Sepsis

The objective of this study was to determine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in septic patients with neutropenia.. Twenty consecutive septic patients were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days (group G). They were compared with 14 septic patients treated earlier without rhG-CSF (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL. Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an indicator of the tissue injury were evaluated in group G.. In group G, TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL-6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI. Consequently, the APACHE II score and MOF index improved. In group N, however, CRP showed no change concomitant with the APACHE II score and MOF index.. Administration of rhG-CSF attenuates inflammatory responses without inducing tissue injury in septic patients with neutropenia.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Lenograstim; Leukocyte Count; Leukocyte Elastase; Male; Middle Aged; Multiple Organ Failure; Neutropenia; Recombinant Proteins; Sepsis; Tumor Necrosis Factor-alpha

Several studies have shown that interleukin-8 (IL-8) causes a rapid granulocytosis with the release of polymorphonuclear leukocytes (PMN) from the bone marrow (BM) partially responsible for the granulocytosis. This study was designed to quantitate the release of PMN from the BM by IL-8 and measure the transit time of PMN through the marrow after IL-8 administration. The thymidine analogue, 5'-bromo-2'-deoxyuridine (BrdU), was used to label dividing PMN in the marrow and follow their release into the circulation after intravenous IL-8. This allowed us to calculate the transit time of PMN through the mitotic and postmitotic pools of BM. BrdU was infused intravenously into rabbits 24 hours before IL-8 (2.5 microg/kg). IL-8 caused a rapid, transient granulocytopenia (5.9 +/- 0.4 at baseline v 0.2 +/- 0.06 x 10/9L at 5 minutes, P < .05) followed by granulocytosis (8.4 +/- 0.1 at 30 minutes, P < .05) associated with an increased number (0.3 +/- 0.1 at baseline v 1.2 +/- 0.6 x 10(9)/L at 30 minutes, P < .05) and percentage of band cells (P < .05), as well as a rapid increase in the number of BrdU-labeled PMN (PMNBrdU) in the circulation (0.09 +/- 0.05 at baseline to 1.5 +/- 0.6 x 10(9)/L at 60 minutes, P < .05). The transit time of PMN through both the mitotic and postmitotic pools of BM was not affected by IL-8. To determine the marrow compartment from which the PMN were mobilized by IL-8, we quantitated PMN movement from the hematopoietic and sinusoidal compartments into the circulation. The fraction of PMNBrdU in both compartments was higher than in the circulating blood (P < .05) and the fraction and number of PMNBrdU in the sinusoids decreased with IL-8 treatment (P < .05). We conclude that the pool of PMN residing in the BM venous sinusoids are rapidly released into the circulation after administration of IL-8.

Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Movement; Female; Injections, Intravenous; Interleukin-8; Leukocytosis; Mitosis; Neutropenia; Neutrophils; Rabbits; Time Factors

We investigated the cytokine network in rabbit lipopolysaccharide (LPS)-induced arthritis, using inhibitors against homologous TNF alpha, IL-1 beta, and IL-8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10 micrograms each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNF alpha and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1 beta and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNF alpha and IL-8, and infiltrating leukocytes were positive for IL-1 beta and IL-1 Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNF alpha and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1 beta was reduced by anti-TNF alpha monoclonal Ab (mAb), IL-1 Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti-TNF alpha mAb or anti-IL-8 IgG. Anti-TNF alpha mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti-IL-8 IgG was less than that of anti-TNF alpha mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNF alpha are the most proximal cytokines and induce subsequent production of IL-1 beta and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.

Topics: Animals; Antibodies, Monoclonal; Arthritis, Experimental; Chemotaxis, Leukocyte; Cytokines; Drug Synergism; Female; Immunoglobulin G; Immunohistochemistry; Inflammation Mediators; Injections, Intra-Articular; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Lipopolysaccharides; Neutropenia; Neutrophils; Rabbits; Receptors, Interleukin-1; Recombinant Proteins; Sialoglycoproteins; Synovial Fluid; Synovial Membrane; Tumor Necrosis Factor-alpha

Plasma levels of IL-1, IL-6, IL-8, IL1-RA, TNF alpha, and G-CSF were prospectively studied during 23 chemotherapy cycles of 20 patients suffering from acute myelogenous leukemia. Increased plasma levels of IL-6, IL-8, and G-CSF were observed in patients with febrile neutropenia and/or major infection. Plasma levels of IL-6, IL-1, TNF alpha and IL-1-RA measured 1 day before and 1 day after the onset of febrile episodes did not accurately predict the development of major infection. In contrast, IL-8 plasma levels were significantly higher in those patients who subsequently developed major infection. The question whether IL-8 plasma levels identify high risk or low risk patients with sufficient specificity and sensitivity has to be answered in large scale clinical trials.

Topics: Adolescent; Adult; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Cytokines; Dacarbazine; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-2; Interleukin-6; Interleukin-8; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Neutropenia; Nimustine; Prospective Studies; Sialoglycoproteins; Tumor Necrosis Factor-alpha; Vincristine

Topics: C-Reactive Protein; Humans; Interleukin-6; Interleukin-8; Leukemia; Neutropenia; Opportunistic Infections

The effect of treatment with interleukin-8 (IL-8), a neutrophil-activating cytokine, was investigated in normal and neutropenic mice infected with a lethal dose of Pseudomonas aeruginosa, Klebsiella pneumoniae, or Plasmodium berghei. Intraperitoneal (i.p.) IL-8 treatment was associated with accelerated death when IL-8 was administered shortly before i.p. infection with P. aeruginosa or shortly after i.p. infection with P. aeruginosa and K. pneumoniae. Histopathological analyses demonstrated a tendency to more severe organ lesions in IL-8-treated mice. Only nonneutropenic mice that received IL-8 shortly before the infectious challenge and at the site of infection were protected by IL-8. Whether IL-8 is protective of or detrimental to the survival of infection appeared to depend on the presence of bacteria at the injection site and on the presence of neutropenia. IL-8 may be an important participant in the cascade of interacting cytokines that is induced by the lethal infectious challenge.

Topics: Animals; Bacterial Infections; Brain; Female; Interleukin-8; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Malaria; Mice; Neutropenia; Peritoneal Cavity; Plasmodium berghei; Pseudomonas Infections

Neutrophils from patients suffering from severe congenital neutropenia (SCN), who were receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF), were investigated in order to analyze the previously described decrease in chemotaxis. This study demonstrated the decreased chemotaxis to five well-known chemoattractants, FMLP, C5a, IL-8, LTB4 and PAF. To further investigate this impairment of patients' neutrophils, receptors and receptor turnover for chemoattractants were examined using flow cytometry. We found 1) increased FMLP receptor and decreased C5a receptor expression, 2) a normal expression of intracellular FMLP receptors after incubation with PMA, 3) increased loss and decreased re-expression of FMLP receptors after incubation with this peptide, 4) normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1 (CD11a/CD18), 5) further signs of in vivo preactivation: high expression of Fc gamma-RI (CD64) and Fc gamma-RII (CD32), decreased expression of Fc gamma-RIII (CD16), increased expression of CD14, and low expression of HLA-DR. These data demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is not due: a) to a decrease in the number of intra- or extracellular FMLP receptors; b) to a decrease of adhesion molecules. However, the decreased chemotaxis could result from an altered FMLP receptor turnover. The relevance of the altered Fc gamma-receptor pattern for the in vivo occurrence of side-effects, e.g. the necrotic vasculitis, of G-CSF treatment is discussed.

Topics: Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Surface; Chemotaxis, Leukocyte; Complement C5a; Fluorescein-5-isothiocyanate; Granulocyte Colony-Stimulating Factor; HLA-DR Antigens; Humans; Immunoglobulin G; In Vitro Techniques; Interleukin-8; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Neutropenia; Neutrophils; Receptors, Fc; Receptors, Formyl Peptide; Receptors, IgG; Receptors, Immunologic; Recombinant Proteins; Reference Values; Tetradecanoylphorbol Acetate

The pathogenesis of acute lung injury in humans is obscure, but lipopolysaccharide (LPS), complement activation, and neutrophils have been implicated. We investigated in rabbits the interaction of small amounts of intravascularly administered LPS (100 ng) with neutrophil chemotactic factors, the synthetic chemotactic peptide formyl-norleucyl-leucyl-phenylalanine (FNLP), and the biologically relevant chemotactic fragments of C5 (C5f). These neutrophil stimuli produce neutropenia when injected intravascularly in rabbits, reflecting neutrophil adherence to vascular endothelium. When LPS was injected with FNLP, the duration of neutropenia was enhanced. Studies with radiolabeled neutrophils infused in vivo demonstrated prolonged neutrophil sequestration within the lung in rabbits that were given FNLP plus LPS, an effect that was visible for 4 h after injection. Morphometric analysis of tissue sections 4 h after infusion confirmed the presence of greater numbers of neutrophils in the lungs of animals receiving LPS and FNLP. When a combination of LPS and chemotactic factors was infused at both zero and 6 h, we found a marked enhancement of lung vascular permeability at 24 h (as assessed by radiolabeled albumin accumulation), an effect not seen with either LPS or chemotactic factor alone. Ultrastructural studies revealed neutrophil sequestration and alteration in endothelial cells in the animals that received the combination of LPS and chemotactic factors. Neutrophil depletion with nitrogen mustard completely abolished the increased vascular permeability seen in animals that received LPS and chemotactic factors. This study suggests that small amounts of intravascularly administered LPS enhance the sequestration of neutrophils within the lung and increase lung vascular permeability and endothelial injury caused by neutrophils stimulated by intravascularly administered chemotactic factors. This mechanism may be relevant to the production of acute lung injury in human beings.

Topics: Albumins; Animals; Autoradiography; Capillary Permeability; Chemotactic Factors; Dose-Response Relationship, Drug; Drug Synergism; Female; Interleukin-8; Lipopolysaccharides; Lung; Male; Microcirculation; Microscopy, Electron; Neutropenia; Neutrophils; Nitrogen Mustard Compounds; Oligopeptides; Rabbits; Time Factors