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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 235 records · Page 13Linked to original sources
PubMed1994

Capillary leak syndrome associated with elevated IL-2 serum levels after allogeneic bone marrow transplantation.

The pathophysiological mechanisms involved in the development of a spontaneous systemic capillary leak syndrome (CLS) are unknown. In contrast, CLS is a well-known side effect of high-dose interleukin-2 (IL-2) therapy in solid tumors. We report on a patient who developed CLS with high serum levels of endogenous IL-2 under immunosuppressive therapy for chronic graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation (BMT). Generalized edema persisted for 10 weeks. The condition resolved after antibiotic therapy of a septic shock with beta hemolyzing streptococci group A. Thus, a latent infection may alter cytokine homeostasis and may cause CLS in BMT patients.

Adult↗
PubMed1994

RUDER--a prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. RUDER Study Group.

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma.

BACKGROUND/AIMS: The pathogenesis of pancreatic cancer is poorly understood. The multigenetic nature of carcinogenesis has been best documented in colon cancer. The relevance of this model was suggested for other epithelial tumors. Only advanced stages of pancreatic cancer are usually detected because of late diagnosis. Analysis of accumulated, diverse genetic changes could allow further understanding of putative mechanisms involved in tumor development. Activated c-Ki-ras oncogene has been shown to be a frequent event. However, additional alterations of tumor suppressor genes are expected. Therefore, concomitant genetic changes of p53 and deleted in colon carcinoma (DCC) in pancreatic carcinoma cell lines and primary tumors were analyzed. METHODS: p53 protein and transcript expression were revealed by immunocytochemistry and immunohistochemistry, immunoassay, and Northern blot analysis. p53 mutations were identified by sequence analysis. DCC expression was investigated by reverse-transcription polymerase chain reaction. RESULTS: p53 overexpression was observed in 9 of 12 cell lines. p53 point mutations were confirmed in seven cell lines overexpressing p53. The majority of cell lines showed concomitant p53 and DCC alterations. Four of 6 primary tumors overexpressing p53 also showed loss of DCC expression. CONCLUSIONS: p53 and DCC genetic changes are associated with pancreatic cancer and the frequently activated c-Ki-ras oncogene. Therefore, the multihit model of carcinogenesis could prove relevant for pancreatic cancer.

Base Sequence↗
PubMed1994

Rat gastric somatostatin and gastrin release: interactions of exendin-4 and truncated glucagon-like peptide-1 (GLP-1) amide.

The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1amide exert their effects on gastric D and G cell by interaction with the same receptor.

Animals↗
PubMed1994

Sodium butyrate induces neuroendocrine cytodifferentiation in the insulinoma cell line RINm5F.

The differentiating agent sodium butyrate inhibits proliferation and stimulates cell-specific hormone expression in rat insulinoma cells. In this study, we investigated the effect of sodium butyrate on neuroendocrine cytodifferentiation in the rat insulinoma subclone, RINm5F. The cells were cultured with 0.5, 1, or 1.5 mM sodium butyrate for up to 72 h. Ultrastructurally, cells cultured with 1 mM sodium butyrate revealed a more differentiated appearance with an induction of cellular compartments involved in regulated insulin secretion. Morphometric analysis showed a significant elevation of neuroendocrine granule density. The total area of the specific granules was increased after incubation with 1 mM sodium butyrate for 48 and 72 h. Proliferation of RINm5F cells was inhibited by sodium butyrate in a dose-dependent manner. DNA production ceased completely within 24 h at 1.5 mM sodium butyrate. This concentration of sodium butyrate increased the cellular insulin content 8.9-fold and the insulin production 2-fold after 72 h. The insulin release was reduced from 79 +/- 3.5% in controls to 37 +/- 5.6% of total in a 24-h incubation period after 3 days of culture with 1.5 mM sodium butyrate. Insulin mRNA levels increased to a maximum of 324% compared with controls after 48 h of culture with 1.5 mM sodium butyrate. Chromogranin A mRNA levels increased to a similar extent (368 +/- 26%), whereas sodium butyrate did not stimulate the expression of synaptophysin, a major membrane component of small neuroendocrine vesicles. In conclusion, our data suggest the selective induction of neuroendocrine cytodifferentiation by sodium butyrate in RINm5F cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1994

Safety of proton pump inhibitors--an overview.

Drug-induced achlorhydria in experimental animals results in excessive hypergastrinaemia, ECL-cell hyperplasia and ECL-cell carcinoidosis. However, these events have not been observed in long-term studies in patients receiving proton pump inhibitors. Serum gastrin levels increase only modestly during acute and long-term treatment. It is concluded that monitoring of serum gastrin levels and of fundic ECL cells is of no clinical relevance even during long-term therapy with proton pump inhibitors. The clinically available proton pump inhibitors such as pantoprazole, omeprazole and lansoprazole are well tolerated, with a low incidence of side-effects. Minor and serious side-effects classified as possibly related to proton pump therapy have been described in up to 2.5% of patients. This is the same order of magnitude as that found in patients treated with H2-receptor blockers and in placebo-treated controls. In most cases, therefore, the observed side-effects are unrelated to the intake of proton pump inhibitors. Minor adverse events include headache, diarrhoea, dizziness, pruritus and rash. Proton pump inhibitors are metabolized mainly in the liver via the cytochrome P450 system and interactions with drugs metabolized by the same system are possible. Evidence is becoming available which suggests that pantoprazole may have less potential to interact with the cytochrome P450 system than the other proton pump inhibitors. In the case of diazepam metabolism, pantoprazole had the least effect on prolongation of the diazepam effect. This may well be an advantage in the clinical use of the drug.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Alpha-subunit and human chorionic gonadotropin-beta immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours.

In the serum of patients with malignant endocrine gastroenteropancreatic (GEP) tumours, both alpha-subunit (alpha-SU), common to all glycoprotein hormones, as well as free beta-subunit of human chorionic gonadotropin (hCG-beta) have been reported to be elevated in a substantial fraction. Both have been discussed as markers of malignancy in these neoplasms. In the present study we evaluated the diagnostic significance of alpha-SU and hCG-beta as serum markers in patients with malignant endocrine gastroenteropancreatic tumours. The study group consisted of 52 patients with endocrine GEP-malignancies (24 nonfunctioning, 23 carcinoid syndromes, four gastrinoma, one glucagonoma), located in the small intestine (n = 29), pancreas (n = 17), colon or rectum (n = 3), retroperitoneum (n = 2) and stomach (n = 1). alpha-SU and hCG-beta immunoreactivity was also assessed in the serum of patients with benign GEP-tumors (five insulinoma, and three gastrinoma). Concentrations of alpha-SU and hCG-beta were determined using two highly sensitive and specific immunoradiometric assays employing two monoclonal antibodies each. In 19 of 52 patients (37%), either alpha-SU (n = 9), hCG-beta (n = 7) or both subunits (n = 3) were elevated. In the subgroup of 24 patients with nonfunctioning GEP-tumours, increased concentrations of either alpha-SU (n = 6) or hCG-beta(n = 3) or both subunits (n = 1) were found in 10 of 24 patients (42%). In four of 23 patients with carcinoid syndrome (17%), either alpha-SU (n = 2), hCG-beta(n = 1) or both subunits (n = 1) were above the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes.

The present paper addresses the question how alpha-glucosidase inhibitors affect glucose homeostasis. To facilitate this already established data on the effects of induced malabsorption on gut hormones such as gastric inhibitory polypeptide (GIP) in connection with preliminary findings which deal with the new incretin hormone glucagon-like peptide 1 (7-36) amide (GLP-1) are discussed. To emphasize the possibly important impact of a regulated GLP-1 release in response to glucosidase inhibitor treatment we evaluate the recently introduced concept of 'glucose competence' of pancreatic beta-cells. The slowing of nutrient (i.e. glucose) absorption by therapeutic means (for example, acarbose) could supplement a new approach in the treatment of type 2 diabetics which would utilize the well-preserved insulinotropic activity of GLP-1 in these patients, its glucagon-lowering effect, and its possible inhibition of gastric emptying rates, the latter helping to reduce the requirement for rapid insulin secretory responses as is intended while using alpha-glucosidase inhibitor treatment.

Animals↗
PubMed1994

A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis.

Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications.

Acute Disease↗
PubMed1994

Incidence and prognosis of obstruction of the left ventricular outflow tract in Liverpool (1960-91): a study of 313 patients.

OBJECTIVE: To determine the incidence of the various types of obstruction of the left ventricular outflow tract in patients born in the five health districts of Liverpool and to compare their prognosis into early adult life. DESIGN: Notes of all patients with obstruction of the left ventricular outflow tract born in the study area between 1960 and 1991 were reviewed. Patients with hypoplastic left ventricle, mitral valve atresia, and those with discordant atrioventricular or ventriculoarterial connections were excluded. Survivors were traced and assessed clinically; eight were lost to follow up. RESULTS: Obstruction of the left ventricular outflow tract occurred in 313 patients (67% male), giving an incidence of 6.1/10,000 live births. The median (range) age at presentation was 13.9 months (0-20 yr). Aortic valve stenosis occurred in 71.2%: subvalve in 13.7%, supravalve in 7.7%, and multilevel in 7.4%. The median (range) duration of follow up was 10.0 (1-29) yr. Aortic regurgitation at presentation occurred more often (p < 0.001) in patients with subvalve stenosis than in those with other types of obstruction, but there was an increased incidence (p < 0.001) at follow up in patients with valve stenosis. Ninety eight patients (31.3%) underwent operation. The reoperation rate was 27% for valve stenosis and 9% for subvalve obstruction. No patients with supravalve stenosis underwent reoperation. The median duration from first operation to aortic valve replacement (17 patients) was 12.3 years. Hazard analysis confirmed that the risk of death was higher in patients presenting at a younger age, with more severe stenosis, and those with subaortic, multilevel obstruction or a syndrome. Hazard analysis also showed that the risk of a clinical event (surgery, balloon dilatation, or endocarditis) was greater in patients who presented at a younger age, with more severe stenosis or aortic regurgitation, and in those with subvalve or multilevel obstruction. CONCLUSIONS: Aortic valve stenosis was the most common type of obstruction. Hazard analysis indicates that the age and severity of obstruction at presentation have a significant effect on survival and freedom from a clinical event. The risk of premature death in patients presenting with moderately severe valve stenosis is reasonably small, but increases considerably in those with subvalve, supravalve, and multilevel obstruction. Patients who present with mild valve stenosis have a good prognosis. The risk of sudden death is less than previous predictions. Patients with subvalve and multilevel obstruction, even when mild at presentation, are more likely to undergo intervention or develop endocarditis than those with valve or supravalve stenosis. Follow up into adult life is essential.

Adolescent↗
PubMed1994

Morphology of left ventricular outflow tract structures in patients with subaortic stenosis and a ventricular septal defect.

OBJECTIVE: To compare the incidence and prognosis of subaortic stenosis associated with a ventricular septal defect and to define the morphological basis of subaortic stenosis. DESIGN: Presentation and follow up data on 202 patients with subaortic stenosis seen at the Royal Liverpool Children's Hospital between 1 January 1960 and 31 December 1991 were reviewed. Survivors were traced to assess their current clinical state. Necropsy specimens of 291 patients with lesions associated with subaortic stenosis were also examined. RESULTS: In the clinical study; 65 (32.1%) of the 202 patients with subaortic stenosis had a ventricular septal defect (excluding an atrioventricular septal defect). 32 of these patients had a short segment (fibromuscular) subaortic stenosis. 33 had subaortic stenosis produced by deviation of muscular components of the outflow tracts. In 17 patients (51.5%) this was caused by posterior deviation or extension of structures into the left ventricular outflow tract, resulting in obstruction above the ventricular septal defect. In the other 16 patients (48.5%) there was over-riding of the aorta with concordant ventriculoarterial connections, (without compromise to right ventricular outflow) producing subaortic stenosis below the ventricular septal defect. Additional fibrous obstruction occurred in 39% of the patients with deviated structures. The age at presentation was lower (P < 0.01) in patients with deviated structures (median (range) 0.4 (0 to 9.2) months) than in those with short segment obstruction (median (range) 4.2 (0 to 84.9) months). The incidence of aortic arch obstruction was higher (P < 0.002) in patients with deviated structures than in those with short segment obstruction (38%). In the morphological study 35 pathological specimens showed obstructive muscular structures in the left ventricular outflow tract either above or below the ventricular septal defect. 16 had either posterior deviation of the outlet septum or extension of the right ventriculoinfundibular fold, or both of these together into the left ventricle. 19 had anterior deviation of the outlet septum into the right ventricle with overriding of the aorta (without compromise to right ventricular outflow). The earliest age at which additional fibrous obstruction was seen was 9 months. The aortic valve circumference was small in 18% of specimens. FOLLOW UP: The median (range) duration of follow up in survivors from the clinical study was 6.6 (1 to 25.7) years. 16 patients with deviated musculature (49%) and 16 with short segment fibromuscular stenosis (50%) underwent operation for subaortic stenosis. Patients with deviated structures were younger at operation than those with short segment stenosis (P < 0.005). Patients with posterior deviation or extension of structures into the left ventricular outflow tract underwent operation for subaortic stenosis more frequently (P < 0.05) than those with anterior deviation of the outlet septum and aortic override. The ventricular septal defect required surgical closure more frequently (P < 0.005) in patients with deviation (93.9%) than in those with short segment obstruction (21.9%). There was no significant difference in the mortality between patients with deviation (27%) and those with short segment obstruction (12%). CONCLUSIONS: 32% of patients in the clinical study with subaortic stenosis had a ventricular septal defect. Only 51% of these had obstructive and deviated muscular structures in the left ventricular outflow tract. These patients had a significantly higher incidence of aortic arch obstruction and required surgery for subaortic stenosis at a younger age than those with short segment obstruction. The ventricular septal defect also required surgical closure more frequently in those patients with deviation. The morphological study defined the two sites of obstruction. The presence or absence and type of deviation should be clearly defined in all patients with a ventricular septal defect,

Aortic Stenosis, Subvalvular↗
PubMed1994

Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.

The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.

Animals↗
PubMed1994

Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues.

The place of the long-acting somatostatin analogue octreotide in the management of symptoms in patients with functional gastroenteropancreatic (GEP) tumors and of growth in patients with metastatic disease is reviewed in this report. Numerous studies indicate that octreotide is, currently, the therapeutic principle of first choice in the symptomatic treatment of patients with carcinoid syndrome, Verner-Morrison syndrome and glucagonoma syndrome but not of insulinoma and gastrinoma patients. A beneficial effect on tumor growth has been demonstrated in 40% of patients with metastatic GEP tumor with stabilization of the disease as the most favorable response. However, further studies have to identify subgroups of patients in whom octreotide alone or in combination with alpha-interferon inhibits tumor growth.

Carcinoid Tumor↗
PubMed1994

Community-based action research in a multi-site prevention project: challenges and resolutions.

This article examines the use of action research strategies over a four-year period in developing and evaluating a prevention program for children and their families. This research has taken place in a low-income multi-cultural neighbourhood in Sudbury. Strategies to foster participation and the practical relevance of findings are described, both for the initial proposal development stage, and for the period after a local program was funded as part of a multi-site evaluation project. After reviewing the challenges inherent in doing action research within a multicultural neighbourhood, and within a multi-site design, we discuss which strategies have worked, and what remains to be resolved.

Affective Symptoms↗
PubMed1994

[Combined treatment of metastatic endocrine tumors of the gastrointestinal tract with octreotide and interferon-alpha].

14 patients with metastatic endocrine gastro-entero-pancreatic carcinoma (6 patients with Carcinoid-syndrome, 3 with gastrinoma and 5 with non-functioning tumor) have been treated with Octreotide 3 x 200 micrograms/die plus Interferon-Alpha 3 x 5 Mio U/week after documented tumor progression during preceding Octreotide-monotherapy. 6 out of 14 patients responded favourable to the treatment: one patient with partial regression and 5 patients with stillstand of tumor growth. In only one patient initial tumor stillstand for 6 months was followed by tumor progression whereas in five patients a beneficial effect on tumor growth could be documented up to 34 months. Inhibition of tumor growth and tumor progression was not necessarily paralleled by respective changes in peripheral hormone levels. These results should initiate a controlled prospective study to prove the hypothesis that in patients with metastasized endocrine gastro-entero-pancreatic tumors the combination of Octreotide and Interferon-Alpha is superior to monotherapy with Octreotide or Interferon-Alpha and to identify those patients who respond to this combined therapy.

Biomarkers, Tumor↗
PubMed1994

Interleukin-8, interleukin-6, and soluble tumour necrosis factor receptor type I release from a human pulmonary epithelial cell line (A549) exposed to respiratory syncytial virus.

The release of interleukin-8 (IL-8), interleukin-6 (IL-6) and the soluble forms of the tumour necrosis factor receptor (sTNF-R) from human pulmonary type II-like epithelial cells (A549) after respiratory syncytial virus (RSV) infection was analysed. RSV infection alone induced a time- and RSV dose-dependent IL-8 and IL-6 release from A549 cells. Furthermore, the soluble form of the TNF-RI was also secreted in a time- and RSV dose-dependent fashion. The soluble TNF-RII was not detected in the cell supernatant of infected epithelial cells. The effect of various cytokines [IL-1 alpha/beta, TNF-alpha/beta, IL-3, IL-6, interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta 2)] and colony-stimulating factors [granulocyte (G)-CSF; granulocyte-macrophage (GM)-CSF] on the IL-8 release from A549 cells was also studied. Our data show that the proinflammatory cytokines IL-1 alpha/beta and TNF-alpha/beta induced an IL-8 release in non-infected A549 cells, and increased the IL-8 release of RSV-infected A549 cells synergistically. In addition, IL-3, G-CSF, IFN-gamma and TGF-beta 2, albeit at high concentrations, induced a low IL-8 release from non-infected A549 cells. The enhanced IL-8 secretion rates were accompanied with elevated cytoplasmic IL-8 mRNA steady state levels, as was shown by Northern blot analysis. Cellular co-culture experiments performed with A549 cells and polymorphonuclear granulocytes or peripheral blood mononuclear cells revealed that increased IL-8 amounts were secreted in the co-culture of non-infected as well as RSV-infected cells. The present study suggests a central role for the airway epithelium during RSV infection with regard to cytokine and cytokine receptor release, resulting in a recruitment and activation of inflammatory and immune effector cells. Our data also suggest that paracrine cytokine networks and cell-cell contact are involved in the regulation of IL-8 secretion within the microenvironment of the bronchial epithelium.

Blotting, Northern↗