Faecal interleukin-8 and tumour necrosis factor-alpha concentrations in cystic fibrosis

Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured in faecal samples from nine patients with cystic fibrosis and nine healthy age matched controls. The patients were assessed with Shwachman score, apparent energy absorption, pancreatic enzyme dosage, simple spirometry, and presence of pseudomonal colonisation. Median (range) wet stool IL-8 and TNF-alpha concentrations in patients were 32,113 pg/g (21,656-178,128) and 3187 pg/g (368-17,611) respectively, compared with < 43.5 pg (IL-8)/g (< 22-4079) and 99 pg (TNF-alpha)/g (< 0.26-231) in controls. IL-8 concentration was negatively correlated with Shwachman score (r = -0.79) and pancreatic enzyme dosage (r = -0.77), but not with energy absorption. Seven patients were mature enough to cooperate with spirometry. Their IL-8 concentrations correlated with percentage predicted forced expiratory volume in one second (r = -0.78). IL-8 concentration was greater in four patients with, than five without, established pseudomonal colonisation: median difference 134,583 pg/g. TNF-alpha concentration was not correlated with measures of disease severity. Faecal IL-8 concentration might reflect the severity of pulmonary inflammation in cystic fibrosis and could provide an easily obtainable marker of disease activity.     

Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

Faecal chymotrypsin concentrations in neonates with cystic fibrosis and healthy controls.

Specimens of meconium and random stools were collected sequentially from 25 healthy newborn babies over the first 8-14 days of life. The stool chymotrypsin concentrations increased from birth to a maximum at 4 days of age and then fell again over the next four days. The lowest individual stool concentrations either side of the four day peak were both, coincidentally, 120 micrograms/g stool. In a second group of 22 newborn babies suspected of meconium ileus and later confirmed to have cystic fibrosis, faecal chymotrypsin concentrations were all appreciably reduced. In eight babies, also with suspected meconium ileus but with negative sweat tests, chymotrypsin concentrations were within the healthy newborn range. Measuring faecal chymotrypsin concentrations is a reliable procedure for identifying pancreatic exocrine insufficiency in the newborn.     

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis.

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.     

Serum interleukin-1 alpha and soluble interleukin-2 receptor concentrations in cystic fibrosis.

Interleukin (IL)-1 and IL-2 may participate in the systemic inflammatory response and hypergammaglobulinaemia observed in patients with cystic fibrosis. Thirty seven patients with cystic fibrosis were compared with 25 normal controls. High IgG and IgM concentrations were associated with more severe pulmonary disease. IL-1 alpha and soluble IL-2 receptor concentrations were higher in the cystic fibrosis group than in the controls and also correlated with concentrations of IgG and IgM. These results suggest that these cytokines may contribute to enhanced immunoglobulin synthesis and silent inflammatory activity in clinically stable patients with cystic fibrosis.     

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.     

Serum interleukin-1 alpha and soluble interleukin-2 receptor concentrations in cystic fibrosis

Interleukin (IL)-1 and IL-2 may participate in the systemic inflammatory response and hypergammaglobulinaemia observed in patients with cystic fibrosis. Thirty seven patients with cystic fibrosis were compared with 25 normal controls. High IgG and IgM concentrations were associated with more severe pulmonary disease. IL-1 alpha and soluble IL-2 receptor concentrations were higher in the cystic fibrosis group than in the controls and also correlated with concentrations of IgG and IgM. These results suggest that these cytokines may contribute to enhanced immunoglobulin synthesis and silent inflammatory activity in clinically stable patients with cystic fibrosis.     

Faecal elastase 1 in children with cystic fibrosis

Recently, a new ELISA kit for determination of elastase 1 in faeces has become commercially available. Studies in patients with chronic pancreatitis have indicated that it is a simple and sensitive test of exocrine pancreatic function. The aim of this study was to assess the clinical value of this new test in cystic fibrosis. A total of 72 children were studied: 27 who were healthy, 22 with cystic fibrosis and 23 with non-pancreatic disorders. Oral pancreatic extracts were not discontinued in the children with cystic fibrosis. A small sample of faeces was collected from each subject for elastase 1 concentration and chymotrypsin activity determination. In all of the healthy children and most of those with non-pancreatic disorders (20/23), elastase 1 concentrations were greater than 500 μg/g; in contrast, the vast majority (20/22) of children with cystic fibrosis had very low values (less than 20 μg/g). The differences between children with cystic fibrosis and the other two groups were highly significant (P < 0.001). With a cut-off level of 132 μg/g, the sensitivity and specificity of faecal elastase 1 for the determination of exocrine pancreatic insufficiency were 96% and 100%, respectively. The specificity of faecal chymotrypsin was 96%, but its sensitivity was not calculated since the children with cystic fibrosis continued to take pancreatic extracts during the study. Conclusion The determination of faecal elastase 1 concentration is a simple and reliable means of assessing exocrine pancreatic function in children with cystic fibrosis. Results are not influenced by non-pancreatic disorders or by enzyme supplementation. Received: 2 July 1996 / Accepted: 15 April 1997     

Increased plasma tumour necrosis factor-alpha concentration in atopic dermatitis.

Plasma tumour necrosis factor-alpha (TNF-alpha) was measured in 15 children with atopic dermatitis, 13 children with bronchial asthma, and 11 healthy controls. Plasma TNF-alpha concentration was increased in atopic dermatitis and the magnitude of the increase was correlated with the severity of the dermatitis but TNF-alpha concentration was not increased in bronchial asthma. A significant correlation was found between plasma TNF-alpha and plasma histamine concentrations in atopic dermatitis. The data suggest that the overproduction of TNF-alpha is associated with increased plasma histamine concentration, and might play a part in the pathophysiological mechanism of atopic dermatitis.     

C reactive protein concentrations in cystic fibrosis.

Serum concentrations of C reactive protein were measured in a cross sectional study of 36 patients with cystic fibrosis and correlated with clinical and radiological assessments. C reactive protein concentration was highly correlated with the Shwachman clinical evaluation score, forced vital capacity as a percentage of the predicted value, and the Chrispin-Norman x ray score. C reactive protein may be a useful objective index of severity of disease in patients with cystic fibrosis.     

Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha and interleukin-1 beta concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy

AIM: To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. METHODS: Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. RESULTS: At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 beta and TNF-alpha concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 beta and TNF-alpha concentrations were not significantly different between the two groups. IL-1 beta, but not TNF-alpha concentrations, in group 2 were even higher than those in group 1, although non-survivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the difference in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha concentrations than the patients whose samples were taken after 6 hours. CONCLUSIONS: Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 beta seems to be a better predictor of HIE than TNF-alpha.     

Plasma vitamin K1 concentrations in cystic fibrosis.

Plasma concentrations of vitamin K1 were similar in 37 patients with cystic fibrosis (median 46 ng/l) and 16 controls (49 ng/l). The plasma concentrations were lower than those previously described in adults, but higher than in neonates. There was no association between an increase in prothrombin time and vitamin K1 plasma concentration.     

新生儿HIE脐血IL-6、IL-8与TNF-α变化及临床意义探讨

为探讨新生儿缺氧缺血性脑病 ( HIE)脐血 IL - 6、IL - 8与 TNF-α的变化及临床意义 ,应用放射免疫法检测了 4 0例 HIE患儿 IL- 6、IL- 8与 TNF- α水平 ,并与 4 0例正常新生儿比较。结果显示与正常新生儿比较 ,HIE患儿与正常对照儿相比脐血IL - 6水平分别为 ( 61.0 4± 2 3 .0 6)对 ( 91.83± 3 7.5 4 ) ng/L ( P<0 .0 1) ,IL - 8分别为( 0 .3 4± 0 .0 9)对 ( 0 .2 6± 0 .0 7) μg/L( P<0 .0 1) ,TNF- α分别为 ( 1.0 3± 0 .3 0 )对 ( 0 .83± 0 .3 1) μg/L( P<0 .0 1) ;而且病情越重改变越明显。因此 ,我们认为 ,围产期窒息与HIE患儿脐血 IL - 6水平减低、IL - 8与 TNF-α水平升高有关 ;它们可能参与了新生儿缺氧缺血性脑损伤的某些发病过程     

Raised serum soluble interleukin-2 receptor concentrations in cystic fibrosis patients with and without evidence of lung disease.

Soluble interleukin-2 receptor (sIL-2R-CD25) concentrations were measured in the sera of 115 children with cystic fibrosis and 45 aged matched controls. Above the age of 4 years children with cystic fibrosis had significantly raised concentrations irrespective of disease status as judged by Shwachman score, lung function, or evidence of pseudomonas colonisation. It is believed that these data indicate that T lymphocyte activation can be detected before there is clinical evidence of lung inflammation due to infection in cystic fibrosis. They support the notion that early use of anti-inflammatory (immunosuppressive) drugs may have a role in delaying the progress of lung damage in cystic fibrosis.     

Interleukin-1 alpha, soluble interleukin-2 receptor, and IgG concentrations in cystic fibrosis treated with prednisolone.

In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril. Renal failure in eight patients was related to young age, low weight, and left-to-right shunt group. Three patients died in congestive heart failure with renal failure. Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.     

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis

Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3rd and 7th days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT > or = 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha > or = 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. It was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease.     

Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis

The study evaluates faecal immunoreactive lipase (IRL) measurement in spot stool samples as an index of exocrine pancreatic function in patients with cystic fibrosis (CF). Stool samples (211) from 183 healthy volunteers (age range: 2 days–14.2 years) showed a normal log distribution of IRL values with a median concentration of 71.4 μg/g (range: 0.53–4160 μg/g). In 156 stool samples from 58 patients with proven CF, the median IRL concentration of 0.4 μg/g (range: 0.003–107 μg/g) was significantly lower (P < 0.001) than that of normal controls. In healthy controls, IRL levels were age related with significantly higher levels (P < 0.001) shortly after birth compared to older children. Stimulation of the exocrine pancreas by oral milk feeding resulted in a significant (P < 0.001) increase in a faecal IRL concentration. Faecal IRL concentrations in meconium were very low and of the same magnitude as in patients with CF. Conclusion Faecal IRL determination had a high diagnostic sensitivity (87%) and excellent diagnostic specificity (97%) in patients with CF. A negative test result (PV_neg: 99%) virtually excluded CF under screening conditions. Received: 20 January 1997 / Accepted in revised form: 22 August 1997     

Role of cytokines (interleukin-1beta, 6, 8, tumour necrosis factor-alpha,and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis

AIM: To investigate whether the serum levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha and the soluble receptor of IL-2 are useful in the diagnosis of neonatal sepsis, and whether their diagnostic power is increased when in combination with classical markers such as C-reactive protein and white blood cell count. METHODS: Blood samples were collected at admission from 40 neonates with suspected infection. Patients were included in different groups according to the bacteriological and laboratory results: Group I consisted of 20 newborns with positive blood cultures and other biological tests suggestive of infection. Group II included 20 neonates with negative blood cultures and biological tests not suggestive of infection. The control group included 20 healthy neonates with no clinical or biological data of infection. RESULTS: Mean values of C-reactive protein were significantly higher in Group I. No differences were found between the groups for white blood cell count, with the exception of the presence of leucocytosis in Group II. Levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha, soluble receptor of interleukin-2, and C-reactive protein were significantly higher in infected neonates than in the control groups. Detection sensitivity and specificity were 80 and 92% for C-reactive protein, 60 and 87% for interleukin-1beta, 61 and 80% for interleukin-6, 62 and 96% for interleukin-8, 54 and 92% for tumour necrosis factor-alpha and 63 and 94% for soluble receptor of interleukin-2. The discriminant analysis showed that the best combination for sepsis diagnosis was C-reactive protein + interleukin-8 + soluble receptor of interleukin-2, with a sensitivity of 85% and a specificity of 97.1%. CONCLUSION: Our study suggests that no individual test can on its own identify infected neonates, and that although the combination of C-reactive protein, interleukin-8 and the soluble receptor of interleukin-2 exhibits a high specificity, its sensitivity is limited.