interleukin-8 and Common-Cold

Morbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy. Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future. The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Topics: Asthma; Bacterial Infections; Bronchitis; Common Cold; Disease Progression; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Neutrophils; Picornaviridae Infections; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus; Tumor Necrosis Factor-alpha

Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures.. Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability.. A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181).. Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Topics: Common Cold; Double-Blind Method; Humans; Interleukin-8; Plant Extracts; Pneumonia; Respiratory System

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

Topics: Adaptive Immunity; Adult; Bifidobacterium animalis; Common Cold; Dietary Supplements; Double-Blind Method; Female; Humans; Immunity, Innate; Inflammation; Interleukin-6; Interleukin-8; Male; Nasal Lavage Fluid; Placebos; Probiotics; Rhinovirus; Virus Shedding

To evaluate the effects of patient-practitioner interaction on the severity and duration of the common cold.. We conducted a randomized controlled trial of 719 patients with new cold onset. Participants were randomized to three groups: no patient-practitioner interaction, "standard" interaction or an "enhanced" interaction. Cold severity was assessed twice daily. Patients randomized to practitioner visits used the Consultation and Relational Empathy (CARE) measure to rate clinician empathy. Interleukin-8 (IL-8) and neutrophil counts were obtained from nasal wash at baseline and 48 h later.. Patients' perceptions of the clinical encounter were associated with reduced cold severity and duration. Encounters rated perfect on the CARE score had reduced severity (perfect: 223, sub-perfect: 271, p=0.04) and duration (perfect: 5.89 days, sub-perfect: 7.00 days, p=0.003). CARE scores were also associated with a more significant change in IL-8 (perfect: mean IL-8 change 1586, sub-perfect: 72, p=0.02) and neutrophil count (perfect: 49, sub-perfect: 12, p=0.09).. When patients perceive clinicians as empathetic, rating them perfect on the CARE tool, the severity, duration and objective measures (IL-8 and neutrophils) of the common cold significantly change.. This study helps us to understand the importance of the perception of empathy in a therapeutic encounter.

Topics: Adult; Attitude of Health Personnel; Common Cold; Empathy; Female; Humans; Interleukin-8; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Patient Satisfaction; Perception; Physician-Patient Relations; Process Assessment, Health Care; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Wisconsin; Young Adult

Echinacea is widely used to treat the common cold.. To assess the potential benefits of echinacea as a treatment of common cold.. Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00065715). Dane County, Wisconsin.. 719 patients, aged 12 to 80 years, with new-onset common cold.. Patients were assigned to 1 of 4 parallel groups: no pills, placebo pills (blinded), echinacea pills (blinded), or echinacea pills (unblinded, open-label). Echinacea groups received the equivalent of 10.2 g of dried echinacea root during the first 24 hours and 5.1 g during each of the next 4 days. Indistinguishable placebo tablets contained only inert ingredients.. The primary outcome was the area under the curve for global severity, with severity assessed twice daily by self-report using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, assessed at intake and 2 days later.. Of the 719 patients enrolled, 713 completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were white. Mean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, -69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, -1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group).. Higher-than-expected variability limited power to detect small benefits.. Illness duration and severity were not statistically significant with echinacea compared with placebo. These results do not support the ability of this dose of the echinacea formulation to substantively change the course of the common cold.. National Center for Complementary and Alternative Medicine, National Institutes of Health.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Common Cold; Echinacea; Female; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Patient Compliance; Physician-Patient Relations; Phytotherapy; Placebo Effect; Plant Extracts; Prospective Studies; Research Design; Severity of Illness Index; Young Adult

Because studies suggest that the dietary supplement conjugated linoleic acid (CLA) has immunomodulatory activities that might benefit common colds, we performed two studies of CLA effects in experimental human rhinovirus (HRV) infection.. The first study explored whether CLA supplementation (Safflorin; Loders Croklaan, BV, Wormerveer, the Netherlands) altered the virological or clinical course of experimental HRV infection, and the second explored whether CLA affected the frequency and severity of HRV cold-associated sore throat and cough. The trials were randomized, double-blinded and placebo-controlled. In total, 50 healthy volunteers aged 18-45 years and susceptible to HRV type-39 (serum neutralizing antibody titre < or = 1:2) participated in study 1 and 80 similar volunteers susceptible to Hank's HRV participated in study 2. Participants ingested CLA 2 g/day or placebo for 4 weeks before and 4 days following intranasal HRV inoculation. The primary endpoint for study 1 was the frequency of colds and for study 2 was the symptom severity scores for sore throat and cough.. In study 1, 10/24 (42%) placebo compared with 7/21 (33%) CLA participants developed colds (P = 0.53). CLA was associated with significant reductions in mean scores for cough (0 CLA versus 0.9 placebo) and sore throat (0.8 CLA versus 2.9 placebo). In study 2, clinical colds developed in 19/33 (58%) placebo and 27/43 (63%) CLA participants. Symptom scores for cough (0.9 CLA versus 1.0 placebo) and sore throat (2.6 CLA versus 3.2 placebo) were not significantly different. Similarly no differences in nasal viral titres or serological responses were found.. CLA dietary supplementation had no consistent effects on the virological or clinical course of experimental HRV colds. A larger study would be required to detect more subtle effects of CLA on HRV cold-associated symptoms.

Topics: Adolescent; Adult; Common Cold; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Interleukin-6; Interleukin-8; Leptin; Linoleic Acids, Conjugated; Male; Medication Adherence; Middle Aged; Rhinovirus; Tumor Necrosis Factor-alpha

Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection.. Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis.. There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer.. The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Topics: Adult; Common Cold; Echinacea; Female; Humans; Interleukin-8; Male; Nasal Lavage Fluid; Neutrophils; Patient Compliance; Phytotherapy; Plant Extracts; Rhinovirus; Treatment Failure

Exacerbations of asthma are often associated with rhinovirus (RV)-induced common colds. During experimental RV-infection in healthy subjects, increased levels of the pro-inflammatory mediator IL-1beta and the anti-inflammatory IL-1 receptor antagonist (IL-1ra) have been found in nasal lavage.. We postulated that the balance between nasal pro- and anti-inflammatory mediator expression is disturbed in asthma, resulting in more extensive inflammation following RV-exposure in asthma.. We determined IL-1ra, IL-1beta, and IL-8 in nasal lavages (days -2, 3, and 6) of non-asthmatics and asthmatics (with and without pre-treatment with the inhaled steroid budesonide) before and after experimental RV16-infection (days 0 and 1).. Following RV16-infection, a significant increase in IL-8 was observed in the placebo- and budesonide-treated asthmatics (P=0.033 and 0.037, respectively), whereas IL-1beta only increased in the two asthma groups combined (P=0.035). A small, but significant, increase in IL-1ra was only observed in the budesonide-treated asthmatics (P=0.047). At baseline, IL-1ra levels were significantly higher in the non-asthmatics than in the placebo-treated asthmatics (P=0.017).. These results demonstrate differences between non-asthmatic and asthmatic subjects in the basal levels of nasal cytokines and their inhibitors, and in the effect of experimental RV-infection on these levels. The results indicate that RV may enhance inflammation more markedly in asthmatics, and suggest that this may in part be explained by lower IL-1ra levels. In addition, the observation that budesonide-treatment may result in higher nasal IL-1ra levels supports the hypothesis that steroids act in part by increasing the endogenous anti-inflammatory screen.

Topics: Asthma; Bronchodilator Agents; Budesonide; Common Cold; Double-Blind Method; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Nasal Lavage Fluid; Rhinovirus; Sialoglycoproteins

Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold. Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells. Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus.. We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16. Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16.. All 12 subjects in each group were infected and developed symptomatic colds. The groups did not differ in the intensity of cold symptoms (median [25th to 75th percentile] score in the clarithromycin group of 25 [5 to 33] versus 21 [11 to 26] in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g [8 to 56 g] versus 12 g [5 to 28 g], P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation. In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold. The changes that we observed did not differ from those in an untreated historical control group.. We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Clarithromycin; Common Cold; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Nasal Lavage Fluid; Neutrophils; Prospective Studies; Rhinovirus; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

Attachment of most rhinovirus subtypes to cells depends on a cellular receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies.. To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans.. Four randomized, double-blind, placebo-controlled trials conducted in January to March 1996.. Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14. A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis.. Tremacamra or placebo was given beginning 7 hours before inoculation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7. Recipients of active treatment received 367 microg of tremacamra per nostril per dose for a total of 4.4 mg/d.. Effect of tremacamra on infection, as determined by virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction was not significant, so results were pooled for the main analysis.. A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=.19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the proportion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight was 32.9 (+/- 8.8) g vs 14.5 (+/- 9.4) g (P<.001 for all comparisons). Tremacamra was not associated with adverse effects or evidence of absorption through the nasal mucosa and did not interfere with development of neutralizing antibody.. Tremacamra reduced the severity of experimental rhinovirus colds. Whether tremacamra will be useful clinically will require further study.

Topics: Administration, Intranasal; Adult; Antibodies; Antibodies, Viral; Common Cold; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Nasal Mucosa; Neutralization Tests; Powders; Rhinovirus; Severity of Illness Index; Solutions; Virus Shedding

Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear.. To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage.. Twenty-seven non-smoking atopic, mildly asthmatic subjects participated in a placebo-controlled, parallel study. A dose of 0.5-2.9 x 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC20 (changes expressed as doubling doses: DD) IL-8 levels were obtained by ELISA, and were expressed in ng/ml.. RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16-treated subjects. Among the 19 RV 16-treated subjects, eight developed severe cold symptoms. Baseline FEV1, did not change significantly during the study in either treatment group (P = 0.99). However, in the RV16-treated subjects there was a decrease in PC20 at day 4, which was most pronounced in those with a severe cold (mean change +/- SEM: -1.14 +/- 0.28 DD, P = 0.01). In addition, IL-8 levels increased in the RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL-8 at day 2 correlated significantly with the change in PC20 at day 4 (r = -0.48, P = 0.04).. We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.

Topics: Adolescent; Adult; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Common Cold; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Forced Expiratory Volume; Histamine; Humans; Interleukin-8; Leukocyte Count; Lung; Male; Nasal Lavage Fluid; Rhinovirus

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Ciliopathies; Cobicistat; Common Cold; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Deprescriptions; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Fatigue; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Leber Congenital Amaurosis; Lopinavir; Methylprednisolone; Optic Atrophies, Hereditary; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tacrolimus

Rhinovirus infection is the most common cause of acute exacerbations of inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, where it provokes steroid refractory and abnormally intense neutrophilic inflammation that can be life threatening. Epidermal growth factor receptor (EGFR) expression correlates with disease severity and neutrophil infiltration in these conditions. However, the role of EGFR signaling in rhinovirus infection is unknown. We measured the key determinants of neutrophilic inflammation interleukin (IL)-8 and ICAM-1 in rhinovirus (RV16 serotype)-infected bronchial epithelial cells, BEAS-2B. RV16 infection stimulated IL-8 and ICAM-1 expression, which was further elevated (2-fold) by transient up-regulation of EGFR levels. Detection of viral RNA by quantitative real time PCR confirmed that enhanced expression was not associated with increased viral replication. EGFR ligands (epiregulin, amphiregulin, and heparin-binding epidermal growth factor) were induced by RV16 infection, and inhibition of metalloproteases responsible for ligand shedding partially suppressed this response. The EGFR inhibitor AG1478, completely blocked IL-8 and ICAM-1 expression to basal levels, as did the specific Erk1/2 inhibitor U0126. The p38 mitogen-activated protein kinase inhibitor SB203580 blocked IL-8 secretion but not ICAM-1 expression, whereas the PI3K inhibitor wortmannin was ineffective in both responses. Kinase inactive K721R EGFR, which is selectively deficient in STAT signaling, reversed RV16 responses associated with EGFR overexpression. In conclusion, RV16 infection rapidly promotes induction of EGFR ligands and utilizes EGFR signaling to increase IL-8 and ICAM-1 levels. These results suggest that targeting EGFR may provide a selective therapy that dampens neutrophil-driven inflammation without compromising essential antiviral pathways mediated by pathogen recognition receptors such as TLR3.

Topics: Amino Acid Substitution; Asthma; Common Cold; Enzyme Inhibitors; ErbB Receptors; Gene Expression Regulation; HeLa Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Ligands; Matrix Metalloproteinases; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neutrophils; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Rhinovirus; RNA, Viral; Signal Transduction; STAT Transcription Factors; Toll-Like Receptor 3

The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.. Prospective cohort study.. Outpatient Department, London Chest Hospital, London, UK.. Thirty-nine patients with COPD.. We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.. A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H. influenzae had higher bacterial loads (10(8.56) cfu/mL vs 10(8.05)cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.. The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.

Topics: Aged; Bacterial Infections; Common Cold; Female; Forced Expiratory Volume; Haemophilus Infections; Haemophilus influenzae; Humans; Interleukin-6; Interleukin-8; Male; Picornaviridae Infections; Pulmonary Disease, Chronic Obstructive; Respiratory System; Respiratory Tract Infections; Rhinovirus; Sputum

Virtually all in vitro studies of the effects of rhinovirus on human airway epithelium have used cells grown under conditions known to produce low levels of differentiation. The relevance of the results to native epithelium is questionable. Here we grew primary cultures of human tracheal or nasal epithelium under three conditions. One condition produced pseudostratified, mucociliary cells virtually indistinguishable from native epithelium. The other two conditions produced undifferentiated squamous cells lacking cilia. Cells were infected for 6 h with rhinovirus-16. After a 24-h incubation period, we determined levels of viral RNA in the cells, numbers of infectious viral particles released in the mucosal medium, expression of a variety of epithelial cytokines and other proteins, release of IL-6 and IL-8, and transepithelial electrical resistance and voltage. After infection, levels of viral RNA in the poorly differentiated cells were 30 or 130 times those in the differentiated. Furthermore, expression of mRNA for inflammatory cytokines, release of infectious particles, and release of IL-6 and IL-8 were closely correlated with the degree of viral infection. Thus well-differentiated cells are much more resistant to viral infection and its functional consequences than are poorly differentiated cells from the same source.

Topics: Cell Differentiation; Cells, Cultured; Common Cold; Electric Impedance; Epithelial Cells; Humans; Immunity, Innate; Interleukin-6; Interleukin-8; Nasal Mucosa; Rhinovirus; RNA, Viral; Trachea

The influence of three important cytokines (IL-8, TNF-alpha, and HuIFN-alpha) on ongoing rhinovirus infections has been examined in vitro, individually or as combinations. TNF-alpha was able to transform traces of HRV infections into full-blown infections. Furthermore, TNF-alpha was able to down-regulate the antiviral action of HuIFN-alpha completely, even at levels of just a few pg/ml. This suggests that the induction of TNF-alpha by HRV may be part of the virus's strategy to minimize the interferon response which is part of the host's immune defence system. However, troxerutin (a flavonoid) was able to neutralize the downregulatory action of TNF-alpha on the HuIFN-alpha system at low levels and re-establish the antiviral activity ascribed to IFN-alpha. IL-8 exerted a minor influence on the interferon system, and had no influence on rhinovirus infections. The in vitro findings are supported, in part, by recent in vivo findings in a common cold pilot study.

Topics: Cell Line; Common Cold; Humans; Hydroxyethylrutoside; Interferon-alpha; Interleukin-8; Rhinovirus; Tumor Necrosis Factor-alpha; Virus Replication

We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness.. The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil-driven inflammation was associated with EVW.. Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL-8, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP).. There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (-1.1, 2.2)x10(4)/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (-8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL-8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55-4.46) ng/mL). Only modest changes were seen in IFN-gamma and no changes were seen in IL-5 or ECP. None of the results was influenced by the atopic status of the subjects in either group.. EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL-8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.

Topics: Common Cold; Enzyme-Linked Immunosorbent Assay; Eosinophils; Forced Expiratory Volume; Humans; Inflammation; Interleukin-8; Nasal Mucosa; Respiratory Sounds; Respiratory Tract Infections; Sputum

Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at COPD exacerbation is unknown. Thirty three patients with moderate-to-severe COPD were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at COPD exacerbation. Within 48 h after the onset of the exacerbation and at baseline, nasal aspirates and induced sputum were taken for rhinovirus reverse transcriptase polymerase chain reaction (RT-PCR) analysis and determination of cytokine levels. Symptoms, recorded on diary cards, were noted and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured. At exacerbation, mean FEV1 and FVC fell significantly from baseline (p<0.001). Ten of 43 exacerbations were associated with rhinovirus infection, detected in induced sputum. In four of these, nasopharyngeal samples contained no detectable rhinovirus. All baseline samples were negative for rhinovirus. The simultaneous presence of increased nasal discharge/nasal congestion (in 26 of the 43 exacerbations) and increased sputum (29 exacerbations) was strongly associated with the presence of rhinovirus (odds ratio 6.15; p=0.036). Total symptom scores were greater for rhinovirus as compared to nonrhinovirus exacerbations (p=0.039). Median baseline sputum interleukin-6 levels rose from 90.2 to 140.3 pg x mL(-1) at exacerbation (p=0.005); the change was greater in the presence of rhinovirus infection (p=0.008). Rhinovirus infection can be detected at chronic obstructive pulmonary disease exacerbation. This is associated with elevation of lower airway interleukin-6 levels, which may mediate lower airway symptom expression during chronic obstructive pulmonary disease exacerbations.

Topics: Aged; Analysis of Variance; Chi-Square Distribution; Common Cold; Female; Forced Expiratory Volume; Humans; Interleukin-6; Interleukin-8; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Sputum; Statistics, Nonparametric; Vital Capacity

Nitric oxide (NO) has been reported to have disparate effects in different viral infections. We conducted a study to determine whether rhinovirus (RV) infection is associated with production of NO, and to assess the effect of NO on RV-induced interleukin-8 (IL-8) elaboration both in vitro in monolayers of BEAS-2B cells, an immortalized respiratory epithelial cell line, and in MRC-5 cells, a diploid human embryonic lung fibroblast cell line, challenged with purified RV type 39, as well as in vivo, in experimental infections with RV type 23. Virus replication was not affected by pretreatment of cell monolayers with any of three different NO donors, and RV infection did not stimulate production of NO. Pretreatment of cell monolayers with either NO donors or inhibitors of NO synthase had no effect on RV-induced IL-8 elaboration measured either 6 or 24 h after virus challenge. Nasal wash specimens from RV-infected volunteers contained low concentrations of nitrite that were not different from the concentrations in specimens from sham-challenged subjects. The concentration of nitrite in these specimens did not change over the course of the subjects' rhinoviral illness. These results suggest that NO does not participate in the pathogenesis of RV infections.

Topics: Cell Line; Common Cold; Epithelium; Fibroblasts; Humans; Interleukin-8; Lung; Nitric Oxide; Nitrites; Rhinovirus; Virus Replication

Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.

Topics: Adolescent; Adult; Allergens; alpha-Macroglobulins; Blood Proteins; Common Cold; Eosinophil Granule Proteins; Female; Humans; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Rhinovirus; Ribonucleases

The purpose of this study was to examine the association between experimental rhinovirus infection and the elaboration of interleukin-8 (IL-8) into nasal secretions of volunteers and to determine the effect of pentoxifylline on IL-8 elaboration and rhinovirus-associated common cold symptoms. Fifty-four subjects with experimental rhinovirus infections and 20 sham-inoculated subjects were studied. Pentoxifylline had no effect on rhinovirus-induced symptoms or nasal-secretion IL-8 concentrations. IL-8 concentrations were significantly greater in nasal secretions from infected symptomatic subjects than in those from infected asymptomatic or sham-challenged subjects on days 2-4 after virus challenge. In infected subjects, there was significant rank correlation between nasal obstruction severity, rhinorrhea severity, and nasal-wash albumin concentrations and the change in IL-8 concentration from baseline on days 2-4 after virus challenge.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Common Cold; Humans; Interleukin-8; Middle Aged; Nasal Lavage Fluid; Pentoxifylline; Rhinovirus

Rhinoviruses are important respiratory pathogens implicated in asthma exacerbations. The mechanisms by which rhinoviruses trigger inflammatory responses in the lower airway are poorly understood, in particular their ability to infect the lower airway. Bronchial inflammatory cell (lymphocyte and eosinophil) recruitment has been demonstrated. IL-8 is a potent proinflammatory chemokine that is chemotactic for neutrophils, lymphocytes, eosinophils, and monocytes and may be important in the pathogenesis of virus-induced asthma. Increased levels of IL-8 have been found in nasal samples in natural and experimental rhinovirus infections. In these studies we therefore examine the ability of rhinovirus to infect a transformed lower airway epithelial cell line (A549) and to induce IL-8 protein release and mRNA induction. We observed that rhinovirus type 9 is able to undergo full viral replication in A549 cells, and peak viral titers were found 24 h after inoculation. Rhinovirus infection induced a dose- and time-dependent IL-8 release up to 5 days after infection and an increase in IL-8 mRNA expression that was maximal between 3 and 24 h after infection. UV inactivation of the virus completely inhibited replication, but only reduced IL-8 protein production and mRNA induction by half, while prevention of virus-receptor binding completely inhibited virus-induced IL-8 release, suggesting that part of the observed effects was due to viral replication and part was due to virus-receptor binding. These studies demonstrate that rhinoviruses are capable of infecting a pulmonary epithelial cell line and inducing IL-8 release. These findings may be important in understanding the pathogenesis of rhinovirus-induced asthma exacerbations.

Topics: Cells, Cultured; Common Cold; Epithelial Cells; Humans; In Situ Hybridization; Interleukin-8; Pulmonary Alveoli; RNA, Messenger; Up-Regulation

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.

Topics: Acute Disease; Adenoviridae; Adult; Asthma; Blood Proteins; Common Cold; Coronavirus; Eosinophil Granule Proteins; Eosinophils; Feasibility Studies; Female; Fibrinogen; Humans; Inflammation; Inflammation Mediators; Influenza A virus; Influenza B virus; Influenza, Human; Interferon-gamma; Interleukin-2; Interleukin-5; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Respiratory Syncytial Viruses; Rhinovirus; Ribonucleases; Sputum; Status Asthmaticus

Neutrophil infiltration is a well-documented early event in the pathogenesis of rhinovirus (RV) infections. To further understand the mechanisms responsible for this neutrophilia, we determined whether interleukin (IL)-8 was present at sites of experimental RV infection in vivo and characterized the mechanism(s) by which RV stimulates IL-8 production in vitro. IL-8 was readily detectable in the nasal washings of all normal volunteers and did not increase with sham nasal inoculation. In contrast, RV infection caused a significant additional increase in nasal IL-8, the levels of which peaked 48-72 h after virus inoculation. RV was a potent stimulator of IL-8 protein production by A549 epithelial-like cells, MRC-5 fibroblasts, and normal human bronchial epithelial cells in vitro. This induction was associated with a significant increase in IL-8 mRNA accumulation and gene transcription. RV also stimulated IL-8 promoter-driven luciferase activity. This stimulation was significantly decreased by mutation of the nuclear factor (NF)-IL-6 site and was completely abrogated by mutation of the NF-kappaB site in this promoter. In addition, NF-kappaB-DNA binding activity was rapidly induced in RV-infected cells. This inducible binding was made up of p65 and, to a lesser extent, p50 NF-kappaB moieties. These studies demonstrate that IL-8 is present in normal nasal secretions and that the levels of IL-8 are further increased after RV infection. They also demonstrate that RVs are potent stimulators of IL-8 production and that this induction is mediated, at least in part, by an NF-kappaB-dependent transcriptional activation pathway. IL-8 may contribute to the pathogenesis of RV infection, and NF-kappaB activation may be a central event in RV-induced pathologies.

Topics: Adult; Cell Line; Cell Nucleus; Common Cold; Epithelial Cells; Fibroblasts; Genes, Reporter; Humans; Interleukin-8; Luciferases; Lung; Nasal Mucosa; NF-kappa B; Polymerase Chain Reaction; Pulmonary Alveoli; Recombinant Fusion Proteins; Rhinovirus; Time Factors; Transcription, Genetic; Transfection

We studied the cytokines IL(interleukin)-1 beta, IL-4, IL-6 and IL-8 in nasal lavage samples from 20 patients with naturally acquired viral rhinitis and 5 healthy controls without nasal complaints. IL-1 beta, IL-6 and IL-8 levels in lavage fluid from the viral rhinitis patients were significantly elevated when compared to control subjects. IL-4 was not measurable in any of the samples. The cytokine levels in secretions from the healthy controls remained stable intraindividually on 5 consecutive sampling days. We suggest that cytokines such as IL-1 beta, IL-6 and IL-8, but not IL-4, are involved in the pathophysiology of the common cold.

Topics: Adult; Case-Control Studies; Common Cold; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1; Interleukin-4; Interleukin-6; Interleukin-8; Male; Nasal Lavage Fluid; Rhinitis