interleukin-8 and Gram-Positive-Bacterial-Infections

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.

Topics: Animals; Cells, Cultured; Chemokine CXCL1; Gram-Positive Bacterial Infections; Host-Pathogen Interactions; Humans; Interleukin-8; Intervertebral Disc Degeneration; Low Back Pain; Nucleus Pulposus; Propionibacterium acnes; Rats; Signal Transduction; Toll-Like Receptor 2; Transcription Factor RelA

Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris. However, clinical association of P. acnes with disease or health has yet to be corroborated experimentally. Current animal models of acne do not closely mimic human disease and have unclear translational value. We have developed a murine model of acne by combining P. acnes inoculation with topical application of a synthetic human sebum. We showed that human sebum promoted persistence of intradermally injected P. acnes with little loss of viability after 1 week and permitted use of more physiologic inoculums. Application of acne-associated P. acnes RT4/5 strains led to development of moderate to severe skin pathology compared with application of health-associated type II P. acnes strains (RT2/6). RT4/5 P. acnes strains uniformly induced higher levels of KC (IL-8), IL-1α, IL-1β, and IL-6 in vitro and in vivo compared with type II P. acnes strains. Overall, our data provide immunopathologic corroboration of health and disease association of clinical P. acnes strains and inform on a platform to query putative virulence factors uncovered by genomic studies.

Topics: Acne Vulgaris; Animals; Bone Marrow Cells; Cell Line; Disease Models, Animal; Female; Gram-Positive Bacterial Infections; Humans; Interleukin-1alpha; Interleukin-6; Interleukin-8; Mice; Mice, Inbred C57BL; Propionibacterium acnes; Skin; Virulence Factors

The cutaneous inflammation associated with acne vulgaris is caused by the anaerobic bacterium Propionibacterium acnes through activation of the innate immune system in the skin. Current standard treatments for acne have limitations that include adverse effects and poor efficacy in many patients, making development of a more effective therapy highly desirable. In the present study, we demonstrate the protective effects of a novel customized α-helical cationic peptide, P5, against P. acnes-induced inflammatory responses in vitro and in vivo. Application of P5 significantly reduced expression of two inflammatory cytokines IL-8 and TNF-α in P. acnes-treated primary human keratinocytes, where P5 appeared to act in part by binding to bacterial lipoteichoic acid, thereby suppressing TLR2-to-NF-κB signaling. In addition, in a mouse model of acne vulgaris, P5 exerted both anti-inflammatory and antimicrobial effects against P. acnes, but exerted no cytotoxic effects against skin cells. These results demonstrate that P5, and perhaps other cationic antimicrobial peptides, offer the unique ability to reduce numbers P. acnes cells in the skin and to inhibit the inflammation they trigger. This suggests these peptides could potentially be used to effectively treat acne without adversely affecting the skin.

Topics: Acne Vulgaris; Animals; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Cells, Cultured; Disease Models, Animal; Gene Expression Regulation; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Keratinocytes; Lipopolysaccharides; Mice; Propionibacterium acnes; Signal Transduction; Teichoic Acids; Tumor Necrosis Factor-alpha

Yashada bhasma (YB) and Tankana (TA) are well characterized minerals used in traditional medicine for the treatment of various skin ailments. Yashada bhasma and TA are a unique preparation of zinc and borax, respectively. The study was conducted to evaluate the in vitro inhibitory effect of YB, TA and its combination (YBTA) on Propionibacterium acne growth and P. acne-induced inflammation.. The minerals were tested for anti-P. acne activity by disc diffusion and broth microdilution methods. The effect of these minerals on P. acne induced TNF-α and IL-8 production and gene expression were studied in THP-1 cells. In vitro toxicity was tested on human keratinocytes (HaCaT) and mouse embryonic fibroblasts (NIH3T3) using MTT assay.. The minimum inhibitory concentrations (MIC values) for YB, TA and YBTA against P. acne were 0.1 ± 0.2, 1.9 ± 0.5 and 0.3 ± 0.5 mg mL(-1) , respectively. YB, TA and YBTA inhibited TNFα by 57.57%, 59.09% and 68.93% and IL-8 production by 48.76%, 47.92% and 51.13% in P. acne-stimulated THP-1 cells, respectively. The CTC50 values on HaCaT and NIH3T3 was 17.44 ± 0.5 and 16.37 ± 0.2 μg mL(-1) for YB, 1023.03 ± 4.0 and 1286.17 ± 4.4 μg mL(-1) for TA and 89.12 ± 2.3 and 111.58 ± 3.5 μg mL(-1) for YBTA, respectively.. The present study revealed the inhibitory effect of YB, TA and YBTA on P. acne growth and inflammation. Clinical studies have suggested the anti-acne benefits of formulations containing YB and TA. The findings obtained from the present in vitro studies provide evidence to support the mechanism of anti-acne properties of YB and TA.

Topics: Acne Vulgaris; Animals; Borates; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Keratinocytes; Mice; Microbial Sensitivity Tests; NIH 3T3 Cells; Propionibacterium acnes; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tumor Necrosis Factor-alpha; Zinc Oxide

An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity.. To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation.. Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation.. The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 μmol L(-1)). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes.. Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Calcium; Cells, Cultured; Erythema; Gram-Positive Bacterial Infections; Helicobacter pylori; Humans; Injections, Intradermal; Interleukin-8; Keratinocytes; Mice, Inbred ICR; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; NF-kappa B; Peptide Fragments; Propionibacterium acnes; Ribosomal Proteins; RNA, Messenger; Skin Diseases, Bacterial; Toll-Like Receptor 2

Chlorophyllin (CHL), a chlorophyll-derivative, exhibits several beneficial properties, including antibacterial, antioxidant, and anticancer activities. However, its antibacterial and anti-inflammatory activities against Propionibacterium acnes have not been described. The antibacterial activity of this compound was evaluated in vitro using the broth microdilution method. CHL had an inhibitory effect on the growth of P. acnes (MIC = 100 μM). In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, CHL significantly decreased interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, decreasing both mRNA and protein levels for these chemokines in THP-1 cells indicating the anti-inflammatory effects of it. To investigate the molecular mechanisms underlying the anti-inflammatory properties of CHL in THP-1 cells stimulated by P. acnes, we used western blotting to analyze the effect of CHL on activation of the nuclear factor (NF)-κB. CHL inhibited P. acnes-induced IL-8 and MCP-1 production via blockade of NF-κB activation in THP-1 cells. Therefore, based on these results, we suggest that CHL is a useful agent to control the growth of P. acnes involved in acne inflammation and prevent acne.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Cell Line; Chemokine CCL2; Chemokines; Chlorophyllides; Down-Regulation; Gram-Positive Bacterial Infections; Humans; Interleukin-8; NF-kappa B; Propionibacterium acnes

Biomarkers and physiomarkers may be useful adjunct tests for sepsis detection in neonatal intensive care unit (NICU) patients. We studied whether measuring plasma cytokines at the time of suspected sepsis could identify patients with bacteremia in centers in which patients were undergoing continuous physiomarker screening using a heart rate characteristics (HRC) index monitor.. Six cytokines were higher in Gram-negative bacteremia (GNB) than in Gram-positive bacteremia or candidemia (GPBC). A cytokine score using thresholds for granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α had 100% sensitivity and 69% positive predictive value (PPV) for GNB. A single cytokine marker, IL-6 < 130 pg/ml, had 100% sensitivity and 52% PPV for sepsis ruled out (SRO). The average HRC index was abnormal in this cohort of patients with clinical suspicion of sepsis and did not discriminate between the final sepsis designations.. In summary, in NICU patients with suspected late-onset sepsis, plasma cytokines can identify those with SRO and those with GNB, potentially aiding in decisions regarding therapy.. Seven cytokines were measured in 226 plasma samples from patients >3 d old with sepsis suspected based on clinical signs, abnormal HRC index, or both. Cases were classified as SRO, clinical sepsis (CS), GPBC, or GNB.

Topics: Bacteremia; Biomarkers; Cytokines; Diagnosis, Differential; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Granulocyte Colony-Stimulating Factor; Heart Rate; Humans; Infant, Newborn; Inpatients; Intensive Care Units, Neonatal; Interleukin-6; Interleukin-8; Neonatal Screening; Retrospective Studies; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Propionibacterium acnes (P. acnes) is a well-known acne-inducing factor which causes inflammatory skin lesions by enhancing cytokine production through toll-like receptor 2 (TLR2). Green tea extract catechin has been documented to possess anti-inflammatory effects. However, little is known about the mechanisms involved or any direct effect of green tea catechin on acne. The present study investigated the therapeutic effects and mechanism of polyphenon-60, also known as green tea catechin compound, on acne in vitro and in vivo. In a clinical study using topical polyphenon-60 treatment, acne patients showed symptomatic improvement with decrease in the number of comedos and pustules. To investigate the mechanism underlying the activity of polyphenon-60 in acne therapy, an in vitro study was performed. We found that polyphenon-60 reduced the levels of P. acnes-enhanced TLR2 and interleukin-8 (IL-8) in THP-1 cells, human monocyte cell line and human primary monocytes. Taken together, these data demonstrate that polyphenon-60 has a therapeutic effect on acne by suppressing inflammation, specifically by inhibiting TLR2 expression and IL-8 secretion via down-regulation of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway and activator protein-1 (AP-1) pathway.

Topics: Acne Vulgaris; Cell Line; Down-Regulation; Flavonoids; Gram-Positive Bacterial Infections; Humans; Immunosuppression Therapy; Interleukin-8; MAP Kinase Signaling System; Monocytes; Phenols; Propionibacterium acnes; Tea; Toll-Like Receptor 2

5-Lipoxygenase (5-LOX) plays key roles in infection and allergic responses. Herein, four 5-LOX-derived lipids comprising 5-hydroxyeicosatetraenoic acid (HETE) attached to phospholipids (PLs), either phosphatidylethanolamine (PE) or phosphatidylcholine (18:0p/5-HETE-PE, 18:1p/5-HETE-PE, 16:0p/5-HETE-PE, and 16:0a/5-HETE-PC), were identified in primary human neutrophils. They formed within 2 minutes in response to serum-opsonized Staphylococcus epidermidis or f-methionine-leucine-phenylalanine, with priming by lipopolysaccharide, granulocyte macrophage colony-stimulating factor, or cytochalasin D. Levels generated were similar to free 5-HETE (0.37 ± 0.14 ng vs 0.55 ± 0.18 ng/10(6) cells, esterified vs free 5-HETE, respectively). They remained cell associated, localizing to nuclear and extranuclear membrane, and were formed by fast esterification of newly synthesized free 5-HETE. Generation also required Ca(2+), phospholipase C, cytosolic and secretory phospholipase A(2), 5-LOX activating protein, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1. 5-HETE-PLs were detected in murine S epidermidis peritonitis, paralleling neutrophil influx, and in effluent from Gram-positive human bacterial peritonitis. Formation of neutrophil extracellular traps was significantly enhanced by 5-LOX inhibition but attenuated by HETE-PE, whereas 5-HETE-PE enhanced superoxide and interleukin-8 generation. Thus, new molecular species of oxidized PL formed by human neutrophils during bacterial infection are identified and characterized.

Topics: Aged; Aged, 80 and over; Animals; Arachidonate 5-Lipoxygenase; Bacterial Infections; Eicosanoids; Female; Gram-Positive Bacterial Infections; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Peritonitis; Phospholipids; Plasmalogens; Signal Transduction; Staphylococcal Infections; Staphylococcus epidermidis; Superoxides; Tandem Mass Spectrometry; Tetradecanoylphorbol Acetate

Acne vulgaris is a skin disease affecting pilosebaceous glands in which Propionibacterium acnes (P. acnes) induced inflammation plays a central role. In order to develop new therapies against the inflammatory events, we evaluated the modulating effect of a new undecyl-rhamnoside, APRC11, on different markers of the inflammation. For this purpose, normal human keratinocytes taken from five healthy donors were pre-incubated for 24 h with APRC11 or Zinc Gluconate (Zn) which was used as reference molecule for its anti-inflammatory properties. Then, keratinocytes were stimulated with P. acnes Membrane Fraction for 6 h, in the presence of either APRC11 or Zn. Different markers were evaluated at mRNA level using a Luminex-based Quantigene array system and at protein level using an ELISA test and a Luminex array system. Results showed that P. acnes significantly increased the expression of IL-1α, IL-1RA, IL-8 and MMP-9. A 24-h treatment with APRC11 prior to the P. acnes stimulation down-regulated the P. acnes-induced cytokines over expression (IL-1α, IL-8 and MMP-9) and up-regulated IL-1RA level in a similar manner than Zn. These regulations were noted at both protein and mRNA levels. In conclusion, the new undecyl-rhamnoside APRC11 is able to down-regulate the expression of molecules implicated in cutaneous inflammation and whose expression is induced by P. acnes, confirming its potential interest in inflammatory acne.

Topics: Acne Vulgaris; Anti-Inflammatory Agents; Antigens, Bacterial; Cells, Cultured; Gene Expression Regulation; Gluconates; Gram-Positive Bacterial Infections; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1alpha; Interleukin-8; Keratinocytes; Matrix Metalloproteinase 9; Propionibacterium acnes; Undecylenic Acids

Odontoblasts, dental pulp fibroblasts and immature dendritic cells (DCs) have been involved in the human dental pulp immune response to oral pathogens that invade dentine during the caries process. How they regulate the inflammatory response to Gram-positive bacteria remains nevertheless largely unknown. In this study we investigated the production of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-8 (CXCL8) in these three cell types upon stimulation with lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria that activates the pattern recognition molecule Toll-like receptor 2 (TLR2). We observed that TNF-alpha gene expression was up-regulated in all LTA-stimulated cell types. IL-1beta gene expression was not or barely detectable in odontoblast-like cells and pulp fibroblasts when stimulated or not, but was expressed in immature DCs and increased upon stimulation. TNF-alpha and IL-1beta proteins were detected in DC culture supernatants but not in odontoblast-like cell and pulp fibroblast ones. CXCL8 gene and protein were clearly expressed and increased in the three cell types upon LTA stimulation. These data indicate that LTA-dependent TLR2 activation in odontoblasts and pulp fibroblasts, in contrast to immature DCs, does not lead to significant TNF-alpha and IL-1beta production, but that all three cell types influence the pulp inflammatory/immune response through CXCL8 synthesis and secretion.

Topics: Cell Differentiation; Cells, Cultured; Dendritic Cells; Dental Pulp; Fetal Blood; Fibroblasts; Gene Expression Profiling; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-8; Lipopolysaccharides; Molar, Third; Odontoblasts; Teichoic Acids; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha

To observe the differences in the cytokine levels in the serum and ascites caused by Gram-positive or Gram-negative bacterial infection in patients with multiple organ dysfunction syndrome (MODS).. The cytokines in the serum and ascites of the patients were examined by enzyme-linked immunosorbent assay in 27 patients with MODS due to Gram-positive (n=13) or Gram-negative (n=14) bacterial infection at day 1.. The levels of LPS and TNF-a were higher in the patients with Gram-negative bacterial infection than in patients with Gram-positive infection (P<0.05), but the levels of IL-6, IL-8 and IL-10 remained comparable between the two groups (P>0.05).. Testing of LPS and TNF-a in the serum and ascites of patients with MODS caused by Gram-positive or -negative bacterial infection may help to identify the pathogens for peritonitis resulting in MODS.

Topics: Ascites; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Multiple Organ Failure; Serum; Tumor Necrosis Factor-alpha

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

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

Acne vulgaris is a multifactorial inflammatory disease of the sebaceous follicles of the face and torso that frequently occurs in adolescence. Initially, acne starts as a non-inflammatory comedo. Subsequently, inflammatory reactions evolve to pustules, granulomas and cystic lesions. Many pathogenic mechanisms have been proposed including sebum excretion, obstruction of hair follicles, impaired keratinization of hair epithelium, bacterial overgrowth and immunological mechanisms; the role of Propionibacterium acnes (P. acnes) is particularly important. Facultative anaerobic gram-positive rods have been implicated in acne pathogenesis. However, the host immune response to P. acnes has not been as yet elucidated.. The aim of the present study is to evaluate the importance of the immune response to P. acnes and the bacteriological factor in the pathogenesis of acne.. P. acnes isolated from acne lesions and healthy volunteers skin were cultured. The peripheral blood mononuclear cells (PBMC) from acne patients or healthy volunteers were stimulated with viable P. acnes, and cytokine production was evaluated using RT-PCR and ELISA.. IFN-gamma, IL-12p40, and IL-8 mRNA and protein production were significantly increased in PBMC from acne patients compared to that from normal donors. However, different P. acnes species isolated from acne lesions or normal subjects showed no difference in cytokines production from acne patients and normal subjects PBMC.. The inflammatory response of acne appears to be attributable to P. acnes-induced host immune response rather than P. acnes strains from normal skin or acne lesions.

Topics: Acne Vulgaris; Adult; Cells, Cultured; Female; Gram-Positive Bacterial Infections; Host-Pathogen Interactions; Humans; Interferon-gamma; Interleukin-12 Subunit p40; Interleukin-8; Leukocytes, Mononuclear; Male; Propionibacterium acnes; Young Adult

Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O2(*-)), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O2(*-) was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O2(*-) was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O2(*-) abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O2(*-) with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O2(*-) production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans.

Topics: Acne Vulgaris; Apoptosis; CD36 Antigens; Cell Line, Transformed; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Keratinocytes; NADPH Oxidases; Nitric Oxide Synthase Type II; Nitrites; Propionibacterium acnes; Reactive Oxygen Species; Signal Transduction

Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations of asthma, and is also known to induce exacerbations of cystic fibrosis and chronic obstructive pulmonary disease. Exacerbations of these diseases are also frequently associated with bacterial and atypical bacterial infection. Alveolar macrophages are the major immune cells in the airways and are important in defence against bacterial infections.. The authors investigated whether rhinovirus modifies cytokine release, the pattern recognition receptor expression and phagocytosis by human alveolar macrophages in response to bacterial products.. Viable rhinovirus was detected in macrophages up to 3 days after exposure and viral RNA expression persisted for 10 days. Infectious but not UV inactivated rhinovirus increased tumour necrosis factor alpha (TNFalpha) and interleukin (IL)8 release by macrophages. In contrast, infectious rhinovirus impaired lipopolysaccharide and lipoteichoic acid induced TNFalpha and IL8 secretion by macrophages. Rhinovirus induced impairment of macrophage antibacterial immune responses did not involve IL10, prostaglandin E(2) or downregulation of Toll-like receptor 2. Furthermore, the macrophage phagocytic response to labelled bacterial particles, but not to latex beads, was impaired.. The authors have identified impairment of cytokine responses to bacterial lipopolysaccharide and lipoteichoic acid by alveolar macrophages in response to infectious rhinovirus. Virus induced impairment of antibacterial host defence has important implications in the pathogenesis of exacerbations of respiratory diseases.

Topics: Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Immunity, Cellular; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; Male; Middle Aged; Phagocytosis; Picornaviridae Infections; Rhinovirus; Teichoic Acids; Tumor Necrosis Factor-alpha

Intrauterine bacterial infections are a well-established cause of pregnancy complications. One key observation in a number of abnormal pregnancies is that placental apoptosis is significantly elevated. First trimester trophoblast cells are known to express TLR1 and TLR2 and to undergo apoptosis following exposure to Gram-positive bacterial peptidoglycan (PDG). Thus, the objectives of this study were to determine whether PDG-induced pregnancy complications are associated with placental apoptosis and to characterize the cellular mechanisms involved. We have demonstrated, using an animal model, that delivery of PDG to pregnant mice early in gestation resulted in highly elevated placental apoptosis, evidenced by trophoblast M-30 and active caspase 3 immunostaining. Using an in vitro model of human first trimester trophoblasts, apoptosis induced by PDG was found to be mediated by both TLR1 and TLR2 and that this could be blocked by the presence of TLR6. Furthermore, in the presence of TLR6, exposure to PDG resulted in trophoblast NF-kappaB activation and triggered these cells to secrete IL-8 and IL-6. The findings of this study suggest that a Gram-positive bacterial infection, through TLR2 and TLR1, may directly promote the elevated trophoblast cell death and that this may be the underlying mechanism of pregnancy complications, such as preterm delivery. Furthermore, the expression of TLR6 may be a key factor in determining whether the response to PDG would be apoptosis or inflammation.

Topics: Animals; Apoptosis; Cell Line, Transformed; Disease Models, Animal; Female; Gram-Positive Bacterial Infections; Humans; Interleukin-6; Interleukin-8; Mice; NF-kappa B; Peptidoglycan; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Premature Birth; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 6; Trophoblasts; Uterine Diseases

Propionibacterium acnes is a key pathogen involved in the progression of inflammation in acne vulgaris. We examined whether vaccination against P. acnes suppressed P. acnes-induced skin inflammation. Inactivation of P. acnes with heat was employed to create a P. acnes-based vaccine. Intranasal immunization in mice with this inactivated vaccine provoked specific antibodies against P. acnes. Most notably, immunization with inactivated vaccines generated in vivo protective immunity against P. acnes challenge and facilitated the resolution of ear inflammation in mice. In addition, antibodies elicited by inactivated vaccines effectively neutralized the cytotoxicity of P. acnes and attenuated the production of proinflammatory cytokine IL-8 in human sebocyte SZ95 cells. Intranasal immunization using heat-inactivated P. acnes-based vaccines provided a simple modality to develop acne vaccines. These observations highlight the concept that development of vaccines targeting microbial products may represent an alternative strategy to conventional antibiotic therapy.

Topics: Acne Vulgaris; Animals; Antibodies, Bacterial; Bacterial Vaccines; Cell Line; Dermatitis; Female; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Mice; Mice, Inbred ICR; Propionibacterium acnes; Sebaceous Glands; Vaccination; Vaccines, Inactivated

Alloiococcus otitidis is a newly recognized species of gram-positive bacteria frequently associated with otitis media. Although immunostimulating activity of this organism has been investigated, little is known about the signaling pathways of chemokine/cytokine induction by this organism. We investigated the role of NF-kappaB and mitogen-activated protein (MAP) kinases in chemokine interleukin-8 (IL-8) production by human peripheral blood mononuclear cells (PBMCs) after stimulation with A. otitidis. The organism could induce in vitro IL-8 production in human PBMCs. I kappa B alpha, NF-kappaB, p38 MAP kinase, p44/42 MAP kinase (ERK1/2) became phosphorylated in PBMCs after stimulation with A. otitidis. And, inhibitors of NF-kappaB (caffeic acid phenylethyl ester), p38 (SB 203580), or ERK1/2 (PD 98059) significantly reduced IL-8 induction by the organism. These results were similar to findings in IL-8 induction by Streptococcus pneumoniae, another gram-positive major middle ear pathogen. Our preliminary study suggests that multiple pathways including NF-kappaB, p38, and ERK1/2 were simultaneously activated, and were associated with IL-8 induction by A. otitidis in human PBMCs.

Topics: Blotting, Western; Enzyme-Linked Immunosorbent Assay; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Leukocytes, Mononuclear; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Otitis Media; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Streptococcus pneumoniae

Topics: Epithelial Cells; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Lung Diseases; Toll-Like Receptors; Viruses

Alloiococcus otitidis has been found to be associated with otitis media with effusion. In this study we investigated whether TLR2 and collectins, surfactant protein A (SP-A) and mannose-binding lectin (MBL), interacted with A. otitidis. Both SP-A and MBL bound to A. otitidis in a Ca(2+)-dependent manner. A. otitidis induced IL-8 secretion from U937 cells and NF-kappaB activation in TLR2-transfected HEK293 cells. However, the cells transfected with the mutant TLR2(P681H) did not respond to A. otitidis. In addition, A. otitidis co-sedimented a recombinant soluble form of the extracellular TLR2 domain, indicating direct binding of the bacterium to TLR2. SP-A and MBL augmented the phagocytosis of A. otitidis by J774A.1 cells. The collectin-stimulated phagocytosis of A. otitidis was significantly attenuated when fucoidan and polyinosinic acid were co-incubated. Immunoblotting analysis revealed that MBL was present in the middle ear effusion from patients with otitis media. These results demonstrate that A. otitidis is a ligand for the collectins and TLR2, and that the collectins enhance the phagocytosis of A. otitidis by macrophages, suggesting important roles of the collectins and TLR2 in the innate immunity of the middle ear against A. otitidis infection.

Topics: Animals; Anti-Bacterial Agents; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Immunoblotting; Interleukin-8; Ligands; Mannose-Binding Lectin; Mice; NF-kappa B; Otitis Media with Effusion; Phagocytosis; Poly I; Polysaccharides; Rats; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; U937 Cells

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

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

The macrolide antibiotic roxithromycin is effective against acne associated with inflammation, but the mechanism by which this is achieved has not been clarified.. We studied the effects of roxithromycin on the production of lipase and neutrophil chemotactic factor by Propionibacterium acnes in vitro.. Roxithromycin significantly inhibited the production of lipase and neutrophil chemotactic factor by P. acnes at a concentration one eighth of the MIC, at which the growth curve of P. acnes is not affected.. One mechanism of the effectiveness of roxithromycin in acne therapy is thought to be the inhibition of bacterial lipase and neutrophil chemotactic factor production by P. acnes.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Lipase; Microbial Sensitivity Tests; Propionibacterium acnes; Roxithromycin

The relationship between cytokines and sepsis has been studied frequently in the intensive care unit (ICU). However, the determination of cytokines in patients as they enter the emergency department (ED) would be more meaningful in predicting the outcome of infection. This study investigated plasma interleukin-8 in the ED as the predictor of bacteremia and sepsis. One hundred patients admitted through the ED with signs of systemic inflammatory response syndrome were studied. Plasma IL-8, IL-6, and tumor necrosis factor (TNF) were assayed by enzyme-linked immunosorbent assay. Patient's data were evaluated using the APACHE II scoring system as predictive factors of morbidity and mortality. Plasma IL-8 (149 pg/mL) detected bacteremia with a positive predictive value of 90.9% and a specificity of 98.7%. Results indicated that the odds ratios (ORs) of bacteremia were 24.78 (P < 0.01, CI = 2.27-270.8), 5.42 (P < 0.05, CI = 1.37-21.4), and 6.05 (P < 0.05, CI = 1.36-26.8) for IL-8, IL-6, and APACHE II, respectively. Occurrence of bacteremia was highly correlated with increases in plasma IL-8 (P < 0.01). IL-8 (OR = 8.25, CI = 1.03-65.9) and APACHE II scores (OR = 12.6, CI = 2.24-70.4) were found to be significantly better predictive factors of mortality (P < 0.01) than IL-6 (OR = 3.60, CI = 0.57-22.7), TNF (OR = 0.24, CI = 0.01-11.0) and age (OR = 1.02, CI = 0.98-1.06). During bacteremia, IL-8 also correlated well with patient use of a ventilator (P < 0.01, OR = 2.43, CI = 2.41-311.19), use of vasopressors (P < 0.05, OR = 2.67, CI = 1.79-370.78), length of stay in the hospital (P < 0.01, OR = 3.14, CI = 1.87-988.31), and stay in the ICU (P < 0.01, OR = 2.51, CI = 2.98-449.80). Measuring IL-8 on patients in the ED with apparent bacterial infections appears to be a reliable predictor of bacteremia and the severity of disease.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Bacteremia; Biomarkers; China; Emergencies; Emergency Service, Hospital; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospitals, University; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Prospective Studies; Treatment Outcome

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

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

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

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

A 67-yr-old patient with septic shock caused by gram-positive infection fell into circulatory collapse. Direct hemoperfusion with an endotoxin-removing column was then carried out for 120 min. As a result, blood pressure and systemic vascular resistance increased significantly during this therapy. Cardiac output changed from hyperdynamic to normodynamic, and plasma endotoxin level decreased. After this treatment, the patient recovered. From this experience, we consider that the endotoxin-removing column may be effective for septic shock patients.

Topics: Aged; Anti-Bacterial Agents; Blood Pressure; Cardiac Output; Endotoxins; Gram-Positive Bacterial Infections; Hemoperfusion; Humans; Interleukin-1; Interleukin-2; Interleukin-6; Interleukin-8; Male; Oxygen; Oxygen Consumption; Polymyxin B; Shock, Septic; Tumor Necrosis Factor-alpha; Vascular Resistance

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Cytokines; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Granulocyte Colony-Stimulating Factor; Growth Inhibitors; Humans; Interleukin-6; Interleukin-8; Leukemia Inhibitory Factor; Lymphokines; Male; Middle Aged; Prognosis; Tumor Necrosis Factor-alpha

Because of their effects on monocytes, monocyte chemotactic proteins-1 and -2 (MCP-1 and MCP-2) may participate in the pathophysiology of sepsis. We measured circulating MCP-1 and MCP-2 levels in 42 septic patients having positive local or blood cultures. MCP-1 and MCP-2 levels were elevated in 24 (57%) and 25 (59%) of 42 septic patients, respectively, compared with healthy volunteers. Both patients with gram-positive and gram-negative infections had elevated MCP-1 plasma levels (P = .0001) and P < .0001), respectively; Mann-Whitney-U test), whereas patients with gram-positive infection, but not those with gram-negative infection, had increased MCP-2 plasma levels (P= .0182). No relative differences in MCP-1 and MCP-2 plasma levels were observed between several subgroups of patients (sepsis v septic shock; survivors v nonsurvivors), although levels of MCP-1 were the highest in patients with the more severe forms of sepsis, ie, those with shock or a lethal outcome. Serial observations showed that MCP-1 and MCP-2 plasma levels remained elevated for at least 48 hours. MCP-1 correlated weakly with interleukin-8 and MCP-2, the correlations for which were most pronounced in patients with septic shock. MCP-2 correlated with interleukin-8, and surprisingly, with the complement activation product C3a; these correlations further improved when analyzing patients with septic shock or when applying gram-positive infections. Thus, our results not only show increased MCP-1 and MCP-2 levels in patients with sepsis, but also suggest that the synthesis and release of MCP-1 and MCP-2 in sepsis are differently regulated in part.

Topics: Chemokine CCL2; Chemokine CCL8; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Monocyte Chemoattractant Proteins; Mycoses; Sepsis; Shock, Septic; Single-Blind Method; Survivors

The effect of 1/10 minimal inhibitory concentrations (sub-MIC) of erythromycin (EM) on human neutrophil chemotactic factor production in comedonal bacteria, Propionibacterium acnes strains, Propionibacterium granulosum strains and coagulase-negative staphylococcus (CNS) strains was assayed using the Boyden chamber method. Sub-MIC of EM significantly suppressed neutrophil chemotactic factor production in all strains of P. acnes, P. granulosum and CNS. Our results suggest that sub-MIC of EM may have an anti-inflammatory action by reducing the inflammatory capacity of comedonal bacteria in inflammatory acne.

Topics: Acne Vulgaris; Erythromycin; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Propionibacterium acnes

Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Bacteremia; Blood Pressure; Complement C3a; Enzyme-Linked Immunosorbent Assay; Factor XII; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-6; Interleukin-8; Lactates; Lactic Acid; Lactoferrin; Leukocyte Elastase; Middle Aged; Pancreatic Elastase; Prekallikrein; Respiratory Distress Syndrome; Shock, Septic