interleukin-8 and Influenza--Human

GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections.

Topics: Adenoviridae; Adenovirus Infections, Human; Adolescent; Adult; Biomarkers; Female; Humans; Influenza A Virus, H3N2 Subtype; Influenza, Human; Interferon-gamma; Interleukin-8; Male; Probiotics; Respiratory Tract Infections; Young Adult

The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and signs of influenza A infection were examined. Adults were intranasally inoculated with a rimantadine-sensitive strain of influenza A HlNl virus and treated with rimantadine or placebo. Viral shedding, secretion weights, symptom scores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were compared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms, in expelled secretion weights, and in levels of IL-6 and IL-8. Compared with placebo, rimantadine treatment reduced viral shedding, systemic symptoms, and levels of IL-8. Days of viral shedding and IL-6 but not IL-8 concentrations were significantly correlated with the other measures of symptoms and signs. These data support a causal relationship between viral replication, cytokine production, and symptom expression, and they suggest that IL-6 may have a role in mediating symptom and sign expression during influenza A infection.

Topics: Adolescent; Adult; Antiviral Agents; Female; Humans; Influenza A virus; Influenza, Human; Interleukin-6; Interleukin-8; Male; Middle Aged; Mucus; Nasal Lavage Fluid; Rimantadine; Statistics, Nonparametric

Exposure to particulate matter (PM) has been associated with increased hospital admissions for influenza. Airway epithelial cells are a primary target for inhaled environmental insults including fine PM (PM

Topics: Antiviral Agents; Cytokines; Epithelial Cells; Humans; Influenza, Human; Interleukin-6; Interleukin-8; NF-kappa B; Orthomyxoviridae; Particulate Matter; Toll-Like Receptor 4

The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary

Topics: Animals; Clostridiales; Disease Models, Animal; Humans; Influenza, Human; Interleukin-8; Mice; Orthomyxoviridae Infections; Pneumococcal Infections; Salmonella Infections, Animal; Salmonella typhimurium; Streptococcus pneumoniae

Based on Janus kinase 1/2-signal transducer and activator of transcription 1(JAK1/2-STAT1) signaling pathway, this study explored the immune mechanism of Maxing Shigan Decoction in alleviating the lung tissue and colon tissue damage in mice infected with influenza virus. The influenza virus infection was induced in mice by nasal drip of influenza virus. The normal group, model group, oseltamivir group, antiviral granule group, and Maxing Shigan Decoction group were designed. After intragastric administration of corresponding drugs or normal saline for 3 or 7 days, the body mass was measured, and lung index, spleen index, and thymus index were calculated. Based on hematoxylin-eosin(HE) staining, the pathological changes of lung tissue and colon tissue were observed. Enzyme-linked immunosorbent assay(ELISA) was used to detect serum levels of inflammatory factors interleukin-8(IL-8) and interferon-γ(IFN-γ), Western blot and real-time quantitative polymerase chain reaction(RT-qPCR) to determine the protein and mRNA levels of JAK1, JAK2, STAT1, interferon regulatory factor 9(IRF9), and IFN-γ in lung tissue and colon tissue. The results showed that after 3 and 7 days of administration, the body mass, spleen index, and thymus index were lower(P<0.05 or P<0.01), and the lung index was higher(P<0.01) in the model group than in the normal group. Moreover, the model group showed congestion, edema, and infiltration of a large number of lymphocytes and macrophages in the lung tissue, irregular structure of colon mucosa, ulceration and shedding of epithelial cells, and infiltration of a large number of inflammatory cells. The model group had higher levels of serum IFN-γ(P<0.01), higher protein and mRNA expression of JAK1, JAK2, STAT1, IRF9, IFN-γ in lung tissue(P<0.05 or P<0.01), higher level of JAK2 protein in colon tissue(P<0.01), and higher protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01) than the normal group. Compared with the model group, Maxing Shigan Decoction group had high body mass, spleen index, and thymus index(P<0.05 or P<0.01), low lung index(P<0.05 or P<0.01), and significant alleviation of pathological injury in lung and colon. Moreover, lower serum level of IFN-γ(P<0.05 or P<0.01), protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue(P<0.05 or P<0.01), JAK2 protein level in colon tissue(P<0.01), and protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01)

Topics: Animals; Colon; Humans; Influenza, Human; Interferon-gamma; Interleukin-8; Janus Kinase 1; Lung; Mice; Orthomyxoviridae; Orthomyxoviridae Infections; RNA, Messenger; Signal Transduction; STAT1 Transcription Factor

Eosinophils participate in the immune response against many pathogens, including viruses. Since mouse eosinophils are susceptible to influenza A virus infection and possess antiviral activity, we evaluated the expression of sialic acid residues in human eosinophils and their response against influenza virus

Topics: Eosinophils; Humans; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interleukin-8; Receptors, Retinoic Acid

To investigate synergistic effect of Reduning (RDN) injection plus ribavirin against severe pneumonia induced by H1N1 influenza A virus in mice.. We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus. We randomly assigned the infected mice into four groups, and treated them with normal saline (NS group), RDN (injection, 86.6 mg/kg), ribavirin (injection, 66.6 mg/kg) or double Ribavirin plus RDN group, the same dosage as used in the single treatments) for 5 d. Lung index and lung pathology were recorded or calculated in terms of the curative effective. Cytokines, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome related protein including caspase-associated recruitment domain (CARD) domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC), caspase-1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3), and reactive oxygen species were simultaneously investigated.. RDN plus ribavirin treatment, not RDN or ribavirin alone, provided a significant survival benefit to the influenza A virus-infected mice. The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury. The combined treatment also reduced the viral titers in mouse lungs and lung index, downregulated their immunocytokine levels, including IL-1β and IL-18, and down regulated the NLRP3, especially the transcription and translation of caspase-1. Meanwhile NS group had significantly higher reactive oxygen species (ROS) expression which could was dramatically reduced by the treatment of RDN plus ribavirin.. Our study showed that RDN combined with ribavirin could protect the mice, and reduce the lung immunopathologic damage caused by severe influenza pneumonia. The mechanism could be that it reduced ROS produce and inhibited NLRP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1β and IL-18.

Topics: Animals; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interleukin-1beta; Interleukin-8; Lung; Mice; Mice, Inbred BALB C; NLR Family, Pyrin Domain-Containing 3 Protein; Pneumonia; Ribavirin

Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log

Topics: Aged; Aged, 80 and over; Antibody Formation; Assisted Living Facilities; Case-Control Studies; Cell Proliferation; Female; Frailty; Hemagglutination Inhibition Tests; Humans; Independent Living; Influenza Vaccines; Influenza, Human; Interferons; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress; T-Lymphocytes; Vaccines, Inactivated

Immune response after intravenous peramivir administration, which is approved for children with influenza infection in Japan, is unclear.. Kinetics of viral load and serum cytokine levels before and after peramivir therapy were analysed in 17 and 8 hospitalized children infected with influenza A and B, respectively. Additionally, haemagglutination inhibition (HI) titre was measured. The first day of hospital admission was defined as day 0.. Serum interleukin (IL)-6 levels in influenza-A-infected children significantly decreased after peramivir administration, unlike in those with influenza B where a decrease on day 1 was followed by an increase on day 2. Serum IL-6 kinetics were similar to viral load kinetics in both influenza-A- and B-infected children between days 0 and 2. Serum IL-8 levels gradually decreased after peramivir therapy in influenza-A-infected children but increased between days 1 and 2 in influenza-B-infected children. Conversely, serum IL-10 levels gradually decreased over time. Serum interferon-γ and granulocyte macrophage colony-stimulating factor levels remained low until day 5. Day 0-4 serum HI titres were <4-fold in all children infected with influenza A or B. Additionally, day 5 HI titres were positive in 4 of 6 influenza A cases and all 3 influenza B cases.. Our results suggest that viral load and inflammatory cytokine kinetics were associated with the antiviral therapy used and that second peramivir administration should be considered in influenza B. The results also highlight antiviral agents as key determinants of the clinical course of influenza virus infection in children.

Topics: Acids, Carbocyclic; Administration, Intravenous; Adolescent; Antiviral Agents; Child; Child, Preschool; Cyclopentanes; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Guanidines; Hemagglutination Inhibition Tests; Hospitalization; Humans; Immunity, Innate; Infant; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza, Human; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Male; Retrospective Studies; Viral Load

One of the key pathophysiologies of H5N1 infection is excessive proinflammatory cytokine response (cytokine storm) characterized by increases in IFN-β, TNF-α, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced cytokine release can occur via an infection-independent mechanism, however, detail of the cellular signaling involved is poorly understood. To elucidate this mechanism, the effect of inactivated (β-propiolactone-treated) H5N1 on the cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL-6 and CXCL8 but not TNF-α, CCL5 or CXCL10. This effect of the inactivated-H5N1 was inhibited by sialic acid receptor inhibitor (α-2,3 sialidase), adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C inhibitors (BIM and Gö6976) and cell-permeant Ca2+ chelator (BAPTA-AM). Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580) and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125, whereas SN-50, an inhibitor of NF-κB, inhibited the effect of virus on mRNA expression of both of IL-6 and CXCL8. Taken together, our data suggest that, without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and α-2,3 sialic acid receptors at the cell membrane of host cells, and involves activation of P2Y6 purinergic receptors.

Topics: Animals; Cell Line; Chickens; Gene Expression Regulation; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Interleukin-6; Interleukin-8; Receptors, Purinergic P2; Respiratory Mucosa; RNA, Messenger; Signal Transduction

Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. Nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. Individuals who will go on to become symptomatic demonstrate increased circulating levels of interleukin (IL)-6, IL-8, IL-15, monocyte chemotactic protein (MCP)-1 and interferon (IFN) gamma-induced protein (IP)-10 as early as 12-29 h post-inoculation (during the presymptomatic phase), whereas challenged patients who remain asymptomatic do not. Overall, the immunological pathways of leucocyte recruitment, Toll-like receptor (TLR)-signalling, innate anti-viral immunity and fever production are all over-represented in symptomatic individuals very early in disease, but are also dynamic and evolve continuously over time. Comparison with simultaneous peripheral blood genomics demonstrates that some inflammatory mediators (MCP-1, IP-10, IL-15) are being expressed actively in circulating cells, while others (IL-6, IL-8, IFN-α and IFN-γ) are probable effectors produced locally at the site of infection. Interestingly, asymptomatic exposed subjects are not quiescent either immunologically or genomically, but instead exhibit early and persistent down-regulation of important inflammatory mediators in the periphery. The host inflammatory response to influenza infection is variable but robust, and evolves over time. These results offer critical insight into pathways driving influenza-related symptomatology and offer the potential to contribute to early detection and differentiation of infected hosts.

Topics: Adult; Asymptomatic Diseases; Chemokine CXCL10; Cytokines; Down-Regulation; Female; Healthy Volunteers; Host-Pathogen Interactions; Humans; Immunity, Innate; Influenza A Virus, H3N2 Subtype; Influenza, Human; Interleukin-15; Interleukin-6; Interleukin-8; Male; Microarray Analysis; Time Factors; Young Adult

To identify plasma biomarkers that can be early predictors of mortality in critically ill patients with primary influenza A/H1N1.. A prospective, multicenter, case-cohort pilot study.. Three academic ICUs.. Fifteen patients with primary influenza A/H1N1 that included seven survivors and eight nonsurvivors. For comparison, age- and gender-matched healthy controls (n = 27) were also studied.. Plasma was prepared from whole blood drawn on ICU admission in patients with influenza (ICU day 1). Microvesicle tissue factor activity, thrombin-antithrombin complexes, and D-dimers were measured as procoagulant markers and markers of activation of coagulation. Plasma cytokine levels were measured on the same blood samples in a subset of 12 patients with influenza using the Luminex Multi-Analyte Profiling system (Luminex Corporation, DeSoto, TX). Patients were followed up for the primary outcome of 28-day mortality.. The average admission Acute Physiology and Chronic Health Evaluation II score of the patients was 25.5 ± 9.3, 60% of patients had shock, and the 28-day mortality rate was 53.3% (n = 8/15). Patients with influenza had dysregulated indices of coagulation and inflammation compared with controls. Among the markers of activation of coagulation measured on ICU day 1, only increased microvesicle tissue factor activity was significantly associated with subsequent influenza-related mortality (5.6 ± 1.2 pg/mL in nonsurvivors vs 1.8 ± 0.8 pg/mL in survivors; p < 0.05). Interleukin-8 was significantly higher in nonsurvivors compared with survivors (71.8 ± 29.1 pg/mL, n = 5 vs 17.3 ± 3.7 pg/mL, n = 7; p < 0.05). In addition, microvesicle tissue factor activity and interleukin-8 levels were significantly and positively correlated (r = 0.60; p = 0.003). Other cytokines, thrombin-antithrombin complexes, and D-dimer were not different between nonsurvivors and survivors and did not correlate with illness severity or mortality.. This study identifies an association between plasma interleukin-8 and microvesicle tissue factor activity measured on admission in patients with severe, primary influenza A/H1N1 infection and subsequent mortality. Thus, these biomarkers may serve as very early prognostic markers for patients with influenza A/H1N1.

Topics: Adult; Biomarkers; Cytokines; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Intensive Care Units; Interleukin-8; Microvessels; Prognosis; Prospective Studies; Thromboplastin

We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n=20) and influenza virus-associated encephalopathy (IE) (n=18) to understand the underlying mechanism of IE. We found that IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n=20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.

Topics: Child; Child, Preschool; Cytokines; E-Selectin; Encephalitis, Viral; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant; Influenza, Human; Interleukin-10; Interleukin-13; Interleukin-1beta; Interleukin-2; Interleukin-5; Interleukin-6; Interleukin-7; Interleukin-8; Leukocyte Elastase; Male; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

During pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established.. The present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women.. This retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-β expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-β) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product β-actin mRNA.. Higher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-β mRNA and IFN-β. These alterations would lead to an imbalance in the immune response of those patients.. Pregnancy-related reductions in IFN-β and TGF-β expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy.

Topics: Adult; Chemokines; Cytokines; Female; Gene Expression Profiling; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interferon-beta; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Severity of Illness Index; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious ecthyma in sheep and goats worldwide. In general, detection of viral DNA and observing ORFV virion in tissues of afflicted animals are two methods commonly used for diagnosis of orf infection; however, isolation of the ORFV in cell culture using virus-containing tissue as inoculum is known to be difficult. In this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully grown in cell culture. We further examined the biochemical characteristic of our isolate, including viral genotyping, viral mRNA and protein expression. By electron microscopy, one unique form of viral particle from ORFV infected cellular lysate was demonstrated in the negative-stained field. Moreover, immunomodulating and anti-influenza virus properties of this ORFV were investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory cytokines IL-8 and TNF-α. And, pre-treatment of ORFV-infected cell medium prevents A549 cells from subsequent type A influenza virus (IAV) infection. Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes at two days prior to IAV infection significantly decreased the replication of IAV. In summary, the results of a current study indicated our Hoping strain harbors the immune modulator property; with such a bio-adjuvanticity, we further proved that pre-exposure of ORFV protects animals from subsequent IAV infection.

Topics: Animals; Cells, Cultured; Coinfection; DNA, Viral; Ecthyma, Contagious; Female; Goat Diseases; Goats; Humans; Influenza A virus; Influenza, Human; Interleukin-8; Mice; Mice, Inbred BALB C; Monocytes; Orf virus; Orthomyxoviridae Infections; Polymerase Chain Reaction; Taiwan; Tumor Necrosis Factor-alpha

There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca(++), Cl(-), prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (p<0.05). IL-6 levels were significantly elevated in influenza A (H1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (p<0.05). TGF-β serum levels discern between healthy controls, influenza A (H1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-β levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-β levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis.

Topics: Adult; Bilirubin; Biomarkers; Community-Acquired Infections; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; Male; Partial Thromboplastin Time; Pneumonia; Prothrombin Time; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; Severity of Illness Index; Transforming Growth Factor beta

The most severe complication of influenza is viral pneumonia, which can lead to the acute respiratory distress syndrome. Alveolar epithelial cells (AECs) are the first cells that influenza virus encounters upon entering the alveolus. Infected epithelial cells produce cytokines that attract and activate neutrophils and macrophages, which in turn induce damage to the epithelial-endothelial barrier. Hepatocyte growth factor (HGF)/c-Met and transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) are well known to regulate repair of damaged alveolar epithelium by stimulating cell migration and proliferation. Recently, TGF-α/EGFR signaling has also been shown to regulate innate immune responses in bronchial epithelial cells. However, little is known about whether HGF/c-Met signaling alters the innate immune responses and whether the innate immune responses in AECs are regulated by HGF/c-Met and TGF-α/EGFR. We hypothesized that HGF/c-Met and TGF-α/EGFR would regulate innate immune responses to influenza A virus infection in human AECs. We found that recombinant human HGF (rhHGF) and rhTGF-α stimulated primary human AECs to secrete IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) strongly and IL-6 and monocyte chemotactic protein 1 moderately. Influenza infection stimulated the secretion of IL-8 and GM-CSF by AECs plated on rat-tail collagen through EGFR activation likely by TGF-α released from AECs and through c-Met activated by HGF secreted from lung fibroblasts. HGF secretion by fibroblasts was stimulated by AEC production of prostaglandin E2 during influenza infection. We conclude that HGF/c-Met and TGF-α/EGFR signaling enhances the innate immune responses by human AECs during influenza infections.

Topics: Alveolar Epithelial Cells; Cells, Cultured; Coculture Techniques; Dinoprostone; ErbB Receptors; Granulocyte-Macrophage Colony-Stimulating Factor; Hepatocyte Growth Factor; Humans; Influenza A virus; Influenza, Human; Interleukin-8; Proto-Oncogene Proteins c-met; Pulmonary Alveoli; Signal Transduction; Transforming Growth Factor alpha

Topics: Acetaminophen; Acute Generalized Exanthematous Pustulosis; Antipyretics; Antiviral Agents; Biopsy; Drug Eruptions; Enzyme-Linked Immunosorbent Assay; Glucocorticoids; Humans; Influenza, Human; Interleukin-22; Interleukin-8; Interleukins; Male; Oseltamivir; Prednisolone; Skin; Treatment Outcome; Up-Regulation

Influenza A virus (IAV) is a worldwide public health problem causing 500,000 deaths each year. Palmitoyl-oleoyl-phosphatidylglycerol (POPG) is a minor component of pulmonary surfactant, which has recently been reported to exert potent regulatory functions upon the innate immune system. In this article, we demonstrate that POPG acts as a strong antiviral agent against IAV. POPG markedly attenuated IL-8 production and cell death induced by IAV in cultured human bronchial epithelial cells. The lipid also suppressed viral attachment to the plasma membrane and subsequent replication in Madin-Darby canine kidney cells. Two virus strains, H1N1-PR8-IAV and H3N2-IAV, bind to POPG with high affinity, but exhibit only low-affinity interactions with the structurally related lipid, palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed the development of inflammatory cell infiltrates, the induction of IFN-γ recovered in bronchoalveolar lavage, and viral titers recovered from the lungs after 5 days of infection. These findings identify supplementary POPG as a potentially important new approach for treatment of IAV infections.

Topics: Administration, Intranasal; Animals; Antiviral Agents; Bronchi; Cell Death; Cells, Cultured; Cytokines; Epithelial Cells; Female; Humans; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Interleukin-8; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Phosphatidylglycerols; Phospholipids; Viral Proteins; Virus Replication

Despite vaccine efforts, influenza outbreaks pose a significant threat to global public health. There are two commercially available seasonal influenza vaccines in the United States: the trivalent inactivated vaccine (TIV), delivered parenterally, and the live attenuated influenza vaccine (LAIV), delivered intranasally. Although both vaccines are generally efficacious, the immunologic mechanisms which contribute to protective immunity are incompletely understood. Thus, we investigated the protracted effects of TIV and LAIV on serum cytokine profiles at 14 and 28 days post-vaccination (when antibody titers are peak) in healthy adults over two influenza seasons. Vaccination with TIV was associated with a small, yet significant, decrease in the levels of both IL-8 and TNF-α at 14 and 28 days post-vaccination. LAIV, however, had no impact on serum cytokine levels. Similarly, analysis of serum antibody titers indicated that TIV recipients had a significantly higher sero-response rate compared to LAIV recipients, as has been previously shown. Finally, we examined the relationship between baseline serum cytokine levels and antibody responses to TIV (LAIV recipients were excluded due to the poor sero-response rate). Interestingly, in TIV recipients pre-vaccination levels of IL-8 were higher in sero-responders compared to non-responders. Collectively, these data suggest that cytokines may influence vaccine outcomes and indicate that parenteral immunization with TIV induces a sustained, systemic cytokine response which lasts for weeks.

Topics: Adolescent; Adult; Antibodies, Viral; Female; Humans; Influenza Vaccines; Influenza, Human; Interleukin-10; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vaccines, Attenuated; Vaccines, Inactivated; Young Adult

Influenza infection is a major cause of morbidity and mortality. Retinoic acid-inducible gene I (RIG-I) is believed to play an important role in the recognition of, and response to, influenza virus and other RNA viruses. Our study focuses on the hypothesis that pandemic H1N1/09 influenza virus alters the influenza-induced proinflammatory response and suppresses host antiviral activity. We first compared the innate response to a clinical isolate of influenza A(H1N1)pdm09 virus, OK/09, a clinical isolate of seasonal H3N2 virus, OK/06, and to a laboratory adapted seasonal H1N1 virus, PR8, using a unique human lung organ culture model. Exposure of human lung tissue to either pandemic or seasonal influenza virus resulted in infection and replication in alveolar epithelial cells. Pandemic virus induces a diminished RIG-I mRNA and antiviral cytokine response than seasonal virus in human lung. The suppression of antiviral response and RIG-I mRNA expression was confirmed at the protein level by ELISA and western blot. We performed a time course of RIG-I and interferon-β (IFN-β) mRNA induction by the two viruses. RIG-I and IFN-β induction by OK/09 was of lower amplitude and shorter duration than that caused by PR8. In contrast, the pandemic virus OK/09 caused similar induction of proinflammatory cytokines, IL-8 and IL-6, at both the transcriptional and translational level as PR8 in human lung. Differential antiviral responses did not appear to be due to a difference in cellular infectivity as immunohistochemistry showed that both viruses infected alveolar macrophages and epithelial cells. These findings show that influenza A(H1N1)pdm09 virus suppresses anti-viral immune responses in infected human lung through inhibition of viral-mediated induction of the pattern recognition receptor, RIG-I, though proinflammatory cytokine induction was unaltered. This immunosuppression of the host antiviral response by pandemic virus may have contributed to the more serious lung infections that occurred in the H1N1 pandemic of 2009.

Topics: Antiviral Agents; DEAD Box Protein 58; DEAD-box RNA Helicases; Humans; Immunity, Innate; Immunosuppression Therapy; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Interferon-beta; Interleukin-6; Interleukin-8; Lung; Organ Culture Techniques; Pandemics; Receptors, Immunologic

The severity of avian influenza H5N1 disease is correlated with the ability of the virus to induce an over production of proinflammatory cytokines from innate immune cells. However, the role of each virus gene is unknown. To elaborate the function of each virus gene, the recombinant vaccinia virus inserted HA and NS gene from the 2004 H5N1 virus were used in the study.. U937 cells and PMA activated U937 cells were infected with recombinant vaccinia virus inserted with HA or NS gene. The expressions of HA and NS proteins in cells were detected on immunofluorescence stained slides using a confocal microscope. The cytokine productions in the cell supernatant were quantitated by ELISA.. The recombinant vaccinia virus inserted with HA genes induces the production of IL-1beta, MIP-1alpha, IL-8 and IL-18 cytokines from PMA activated U937 cells significantly more than cells infected with wild type vaccinia, whereas the recombinant vaccinia virus inserted with NS genes it was similar to that with the wild type vaccinia virus. However, there was no synergistic nor antagonistic effect of HA genes and NS genes in relation to cytokines production.. Only the HA gene from the 2004 H5N1 virus induces IL-1beta, MIP-lalpha, IL-8 and IL-18 cytokine productions from activated U937 cells. The same HA gene effect may or may not be the same in respiratory epithelial cells and this needs to be explored.

Topics: Adjuvants, Immunologic; Chemokine CCL3; Cytokines; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Genes, Viral; Genetic Vectors; Hemagglutinins, Viral; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Interleukin-18; Interleukin-1beta; Interleukin-8; Microscopy, Confocal; Tetradecanoylphorbol Acetate; U937 Cells; Vaccinia virus; Viral Nonstructural Proteins

Avian-lineage H3N2 canine influenza virus (CIV)-associated respiratory disease, which can be fatal, emerged in South Korean dogs in 2007. We show here that dogs experimentally infected with CIV only developed respiratory tract diseases, as no extrapulmonary lesions and virus antigens were detected. This differs from the multiorgan diseases that avian influenza H5N1 induces in small experimental animals. However, the CIV-infected dogs developed a distinctively severe, long-persistent bronchointerstitial pneumonia, which differs from the acute but short-term bronchopneumonia that human (H1N1 and H3N2) influenza cause in rodents and ferrets. Histopathology and in situ TUNEL assays revealed that the neutrophils infiltrating the lesions were undergoing apoptosis, which probably reflects the attempts by the body to maintain appropriate numbers of neutrophils for defense against secondary bacterial infections. Our observations suggest that neutrophils along with the related chemoattractant cytokines (TNF-alpha, IL-1 and IL-8, etc.) may play a key role in the pathogenesis of H3N2 CIV in dogs.

Topics: Animals; Apoptosis; Dog Diseases; Dogs; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza, Human; Interleukin-1; Interleukin-8; Lung; Neutrophils; Orthomyxoviridae Infections; Trachea; Tumor Necrosis Factor-alpha

We postulate that hypercytokinemia plays a role in immunopathogenesis of severe human influenza.. We prospectively studied 39 consecutive patients who were hospitalized with severe influenza A virus infection. On laboratory confirmation of the diagnosis, paired acute-phase (obtained at hospital admission) and convalescent-phase (obtained >10 days after hospital admission) plasma samples were collected for assay of 11 cytokines and chemokines (interleukin [IL] 1 beta; IL-6; IL-10; IL-12p70; tumor necrosis factor alpha; IL-8; monokine induced by interferon [IFN]-gamma; IFN-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation, normal T cell-expressed and secreted; and IFN-gamma) using cytometric bead-array analysis and enzyme-linked immunosorbent assay. Simultaneously, virus concentration in the acute-phase nasopharyngeal aspirate was determined using real-time quantitative reverse-transcriptase polymerase chain reaction. Intracellular signaling molecules regulating lymphocyte activation, phospho-p38 mitogen-activated protein kinase and phospho-extracellular signal-regulated protein kinase in CD4+ and CD8+ T lymphocytes were studied in the acute-phase samples using flow cytometric analysis and were compared with results for samples from healthy control subjects.. Statistically significant increases in plasma IL-6 (3.7-fold increase), IL-8 (2.6-fold increase), IFN-induced protein 10 (4.9-fold increase), and monokine induced by IFN-gamma (2.3-fold increase) concentrations were detected during acute illness (P < .01 for all, by Wilcoxon signed-rank test); the highest concentrations were observed on symptom days 3 and 4. Corresponding plasma cytokine and chemokine concentrations and nasopharyngeal viral loads showed statistically significant correlations (rho = 0.41, 0.49, 0.54, and 0.46, respectively; P < or = .01). Phospho-p38 mitogen-activated protein kinase expression in CD4+ lymphocytes was increased, correlating with cytokine concentrations (e.g., for IFN-induced protein 10, rho = 0.78; P < .01); phospho-extracellular signal-regulated protein kinase was suppressed. Advanced age and comorbidity were associated with aberrant IL-6, IL-8, and monokine induced by IFN-gamma responses (P < .05, by Mann-Whitney U test). An elevated IL-6 concentration was independently associated with prolonged hospitalization (hospitalization for >5 days; P = .02), adjusted for age, comorbidity, and virus load.. Hypercytokinemia (of proinflammatory and T helper 1 cytokines) is detected in severe influenza, correlating with clinical illness and virus concentration. Hyperactivation of phospho-p38 mitogen-activated protein kinase (in T helper cells) is possibly involved. Early viral suppression may attenuate these potentially deleterious cytokine responses.

Topics: Adolescent; Adult; Chemokine CXCL9; Cytokines; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Influenza A virus; Influenza, Human; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Tumor Necrosis Factor-alpha

Influenza-associated encephalopathy is reported to be frequent in Japan and East Asia. No evaluating markers except interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and no likely pathological mechanism for the disease have yet been elucidated.. In this study, influenza-associated encephalopathy was defined by clinical symptoms, and the use of an anti-influenza antibody test and/or influenza antigen detection kits, as well as computed tomography and/or magnetic resonance imaging. The levels of proinflammatory cytokines, acute phase proteins, endothelial markers and cytochrome c were compared in sera from 11 patients with and 42 without encephalopathy.. Cytochrome c concentration in sera from patients with encephalopathy was markedly increased compared with that from patients without encephalopathy and normal controls. Although levels of several other proinflammatory cytokines and acute phase proteins such as TNF-alpha and IL-8 were also elevated in patients with influenza virus infection, the difference between those with and without encephalopathy, though significant, was less dramatic. The mean serum concentration of cytochrome c in 11 patients with encephalopathy, consisting of four deceased, four with and three without residual central nervous system sequelae, was 26.7 +/- 19.5 ng/mL on admission. In contrast, cytochrome c levels in 42 patients without encephalopathy were 0.3 +/- 0.7 ng/mL.. The present results indicate that cytochrome c is a useful marker to follow patients with influenza-associated encephalopathy and suggest that an apoptosis of cells in several organs including the cerebrum and liver under the influence of hypercytokinemia is a possible mechanism of the disease.

Topics: Apoptosis; Child; Child, Preschool; Cytochromes c; Cytokines; Encephalitis, Viral; Female; Humans; Infant; Influenza, Human; Interleukin-8; Male; Tumor Necrosis Factor-alpha

Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability.. Monocytes were isolated by Vacutainer(R), BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS(R), Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants.. Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL-1 and 250 pg mL-1) or Cp (733 pg mL-1 and 268 pg mL-1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3-5-fold higher (1797 pg mL-1 and 725 pg mL-1). Interleukin-10 was not produced by infected monocytes.. The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes.

Topics: Antibodies; Chlamydophila Infections; Coronary Artery Disease; Cytomegalovirus Infections; Humans; Influenza A virus; Influenza, Human; Interleukin-10; Interleukin-6; Interleukin-8; Monocytes; Thromboplastin; Virus Diseases; Whole Blood Coagulation Time

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)-6, IL-8, IL-11, and interferon-gamma (IFN-gamma) levels in nasopharyngeal aspirates (NPA) from non-asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL-11 in NPA from asthmatic children were significantly higher than those from non-asthmatic children with RSV infection, and RSV infection enhanced the IL-11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL-6 than that of children with IFAV infection. There was little difference in the IL-8 and IFN-gamma levels between asthmatic and non-asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL-11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL-6 production in RSV infection compared with IFAV infection.

Topics: Asthma; Biomarkers; Bronchiolitis, Viral; Child Welfare; Child, Preschool; Cytokines; Female; Humans; Infant; Infant Welfare; Influenza A virus; Influenza, Human; Inhalation; Interferon-gamma; Interleukin-11; Interleukin-6; Interleukin-8; Male; Nasopharynx; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Statistics as Topic

Both virus-mediated damage to airway tissues and induction of pro-inflammatory cytokines such as interleukin-8 (IL-8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL-8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n = 198) or from healthy uninfected infants (n = 31) were analysed for IL-8. Nasal wash IL-8 was positively related to age in uninfected children (rs = 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL-8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL-8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL-8 levels and symptom scores during infections with rhinovirus (rs = 0.56, p < 0.001) or influenza A (rs = 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationship between the generation of IL-8 and symptoms during acute community-acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL-8 production appear to contribute to the generation of clinical symptoms.

Topics: Age Factors; Fluorescent Antibody Technique, Direct; Humans; Infant; Infant Welfare; Infant, Newborn; Influenza A virus; Influenza, Human; Interleukin-8; Nasal Lavage Fluid; Picornaviridae Infections; Prospective Studies; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Rhinovirus; Severity of Illness Index; Statistics as Topic

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

The role of cytokines in the pathogenesis of pneumonia is still poorly understood. In a previous study the diagnostic value of measuring blood concentrations of interleukin 6 and interferon gamma was established. In the present study the value of blood concentrations of interleukin 8, granulocyte-colony stimulating factor, and lactoferrin as markers of bacteraemic pneumonia is evaluated.. The circulating concentrations of interleukin 8 (IL-8), granulocyte-colony stimulating factor (G-CSF), and lactoferrin were measured in 14 patients with bacteraemic pneumococcal pneumonia and 49 patients with atypical pneumonia or influenza A infection using enzyme immunoassays.. Serum G-CSF concentrations were higher in the group with bacteraemic pneumococcal pneumonia, and G-CSF values correlated with the white blood cell count and levels of C-reactive protein (CRP). The levels of IL-8 were higher in the group with bacteraemic pneumococcal pneumonia than the groups with Chlamydia pneumonia, Legionella pneumonia, or influenza A infection, but there was no difference when compared with the group with Mycoplasma pneumonia. A white blood cell count of > 15 x 10(9)/l was highly suggestive of bacteraemic pneumonia. The concentrations of lactoferrin were raised in all groups except those with influenza A infection, but no difference was found between the different aetiological groups. A correlation was found between lactoferrin and white blood cell counts.. Serum G-CSF and IL-8 concentrations are potential markers of bacteraemic pneumonia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Chlamydia Infections; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Humans; Influenza A virus; Influenza, Human; Interleukin-8; Lactoferrin; Legionnaires' Disease; Leukocyte Count; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal