Concentrations Of IL-1alpha Research Articles

CIRCULATING SASP FACTORS ARE ELEVATED IN PATIENTS WITH POSTOPERATIVE DELIRIUM

Abstract Aging, a major risk factor for delirium, is associated with accumulation of senescent cells in many tissues of the body. Senescent cells produce a host of proinflammatory and tissue remodeling factors collectively termed the senescence-associated secretory phenotype (SASP), which are secreted into circulation. The relationship between increased senescent cell burden and risk of delirium is not known. This study aimed to determine whether changes in circulating SASP proteins are associated with increased risk of postoperative delirium in cognitively intact older adults. Participants were recruited among patients scheduled for surgical or transcatheter aortic valve replacement, and blood was obtained at the presurgical visit. SASP factors were measured using commercially available multiplex magnetic bead immunoassays based on Luminex xMAP multianalyte profiling platform and analyzed on a MAGPIX system. Activin A concentration was determined by a Quantikine ELISA kit. Delirium cases were identified by manual chart abstraction, utilizing the problem list, ICD-10 codes, clinical notes, and nursing flowsheets. Eight of 62 (12.9%) of patients within the cohort developed postoperative delirium. Length of stay was significantly longer for patients who developed delirium (10.6 days) versus patients without delirium (6 days). Concentrations of SASP factors Activin A and PAPP-A were significantly higher in plasma of patients with delirium vs. those who did not develop delirium. IL-1 alpha concentration was significantly lower in patients with delirium vs without delirium. Other SASP factors measured were not statistically different between groups. More study is needed to determine whether these changes are directly related to increased senescent cell burden.

Immune thrombocytopenia: serum cytokine levels in children and adults

BackgroundImmune thrombocytopenia (ITP) is an immune-mediated platelet disorder in which autoantibody-coated platelets are removed from the blood by monocytic phagocytes and there is impaired platelet production. There is a delicate balance of specific cytokine levels, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. This study was designed to investigate the differences in Th cytokine levels between children and adults with newly diagnosed ITP and to compare these profiles to those found in healthy, age-matched controls.Material/MethodsThe concentration of IL-1α, IL-2, IL-3, IL-4, IL-6, IL-10, TNF-α, IFN-α, and IFN-γ in serum specimens was analyzed by enzyme-linked immunosorbent assay.ResultsAt the time of ITP diagnosis, children showed significantly lower serum levels of interleukin IL-2 and tumor necrosis factor TNF-α and higher serum level of IL-3 than healthy controls. Serum level of IL-4 in adult ITP patients was higher than those in control subjects. When compared with adults, children with ITP had lower serum level of IL-4, IL-6 and IFN-γ, and higher level of IFN-α.ConclusionsSignificant differences in serum cytokine levels between pediatric patients and healthy controls indicate that cytokine disturbances – especially changes in IL-2, IL-3 and TNF-α – might be involved in the pathogenesis of newly diagnosed ITP. TNF-α is the most informative variable for discrimination between healthy children and those with ITP.

Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls

BackgroundObesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters.MethodsPlasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD).ResultsCompared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients.ConclusionsThe results suggest that both MO and CRC have low-grade inflammation as part of their etiology.

Effect of a Mangosteen Dietary Supplement on Human Immune Function: A Randomized, Double-Blind, Placebo-Controlled Trial

The effect of a mangosteen product containing multivitamins and essential minerals was tested on immune function and well-being in healthy adults. A randomized, double blinded, placebo-controlled study was conducted in 59 healthy human subjects (40-60 years old). Changes from baseline immune function were measured after a 30-day consumption of the mangosteen product and the placebo. The subjects' self-appraisal of their health status was also surveyed. A xanthone-rich mangosteen product intake increased mean values for peripheral T-helper cell frequency (P = .020) and reduced the serum C-reactive protein concentration (P = .014). Increases in peripheral CD4/CD8 double-positive (DP) T-cell frequency and serum complement C3, C4, and interleukin (IL)-1alpha concentrations were significantly higher in the experimental group than in the placebo group (DP, P = .038; C3, P = .017; C4, P = .031; IL-1alpha, P = .006). At the end of study, serum IL-1alpha and IL-1beta concentrations in the study group were significantly higher than that in the placebo group (IL-1alpha, P = .033; IL-1beta, P = .04). Furthermore, more participants in the experimental group reported greatly improved overall health status compared with participants receiving placebo (P = .001). The results indicated that the intake of an antioxidant-rich product significantly enhanced immune responses and improved the subject's self-appraisal on his or her overall health status.

Clinical Features, Adenovirus Types, and Local Production of Inflammatory Mediators in Adenovirus Infections

Adenovirus infection manifests in many ways, with respiratory and gastrointestinal symptoms predominating. We performed a retrospective chart review on children evaluated at our center who had a nasal wash culture positive for adenovirus. Archived nasal washes were retrieved. Polymerase chain reaction for 15 respiratory viruses was performed on these samples. Patients who were coinfected with another virus were excluded. Adenovirus typing was performed using polymerase chain reaction primers directed at the conserved hexon gene. Bead proteomics was used to measure concentrations of inflammatory mediators. Seventy-eight patients were infected only with adenovirus. The clinical diagnosis was upper respiratory infection in 60%, pneumonia in 18%, febrile seizure in 8%, and bronchiolitis in 6%. Subgroup-C and B1 infections were most common. Seventy percent of patients with upper respiratory infection and all 5 patients with bronchiolitis had a subgroup-C infection; pneumonia was caused by subgroup-B1 and C viruses. Compared with asymptomatic control patients, adenovirus infected patients had higher nasal wash concentrations of interleukin (IL)-1alpha, IL-6, inducible protein-10, macrophage inflammatory protein-1alpha, tumor necrosis factor alpha, monokine induced by gamma interferon, and interferon-alpha (P < 0.05). In addition, we found that IL-8 and IL-1alpha (P < 0.05) were higher in the nasal washes obtained from hospitalized patients than in nonhospitalized patients. Adenovirus infection causes an array of clinical disease and is associated with local production of several proinflammatory cytokines. The observation that nasal wash IL-8 and IL-1alpha concentrations were higher in patients requiring hospitalization suggests that these mediators contribute to disease severity.

Post-natal Changes in Testicular Concentrations of Interleukin-1 Alpha and Beta and Interleukin-6 during Sexual Maturation in Bulls

Based on observations in laboratory animals interleukins could be regulators of testicular development. The objects of this study were to see if interleukins (IL-1 and IL-6) are present in the developing bull testis and to establish the temporal patterns of concentrations of IL-1 and IL-6 in the bovine testis during development. Separate groups of six bull calves were castrated every 4 weeks from 5 to 33 weeks of age, and at 56 weeks of age. Mean testicular IL-1 alpha concentrations decreased (p < 0.01) from 5 to 9 weeks of age and 13 to 21 weeks of age. Mean testicular IL-1 beta concentrations decreased (p < 0.01) from 13 to 17 weeks of age and from 29 to 33 weeks of age. Mean IL-1 bioactivity increased from 13 to 17 weeks of age, decreased to 21 weeks, increased to 25 weeks, decreased to 29 weeks and decreased from 33 to 56 weeks of age (p < 0.05). Mean testicular IL-6 concentrations decreased (p < 0.05) from 9 to 13 weeks of age, increased (p < 0.05) to 21 weeks, decreased (p < 0.05) to 25 weeks, increased (p < 0.05) to 29 weeks and decreased (p < 0.01) to 56 weeks of age. In conclusion, testicular IL-1 alpha, IL-1 beta and IL-6 were found in the bovine testis and concentrations were age dependent. Testicular IL-1 alpha and IL-1 beta concentrations were highest in the early post-natal period; however, IL-1 bioactivity and IL-6 concentrations were greatest in the immediate pre-pubertal period. These findings suggest a functional role for interleukins in testicular development in the bull.

Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol

A validation study of an in vitro skin irritation testing method using a reconstructed human skin model has been conducted by the European Centre for the Validation of Alternative Methods (ECVAM), and a protocol using EpiSkin (SkinEthic, France) has been approved. The structural and performance criteria of skin models for testing are defined in the ECVAM Performance Standards announced along with the approval. We have performed several evaluations of the new reconstructed human epidermal model LabCyte EPI-MODEL, and confirmed that it is applicable to skin irritation testing as defined in the ECVAM Performance Standards. We selected 19 materials (nine irritants and ten non-irritants) available in Japan as test chemicals among the 20 reference chemicals described in the ECVAM Performance Standard. A test chemical was applied to the surface of the LabCyte EPI-MODEL for 15 min, after which it was completely removed and the model then post-incubated for 42 hr. Cell v iability was measured by MTT assay and skin irritancy of the test chemical evaluated. In addition, interleukin-1 alpha (IL-1alpha) concentration in the culture supernatant after post-incubation was measured to provide a complementary evaluation of skin irritation. Evaluation of the 19 test chemicals resulted in 79% accuracy, 78% sensitivity and 80% specificity, confirming that the in vitro skin irritancy of the LabCyte EPI-MODEL correlates highly with in vivo skin irritation. These results suggest that LabCyte EPI-MODEL is applicable to the skin irritation testing protocol set out in the ECVAM Performance Standards.

Nanoemulsions of an anti-oxidant synergy formulation containing gamma tocopherol have enhanced bioavailability and anti-inflammatory properties

The present study investigated whether MicroFluidizer Processor ®-based nanoemulsions of an antio-xidant synergy formulation (ASF), containing delta, alpha and gamma tocopherol influenced inflammation and bioavailability in CD-1 mice. Croton oil was applied to all animals’ right ear lobe to induce inflammation. Auricular thickness was measured after 2 and 6 h after the various treatments. The animal plasma and ear lobes were collected and frozen for bioavailability and cytokine analyses. The ASF nanoemulsions of alpha, delta, or gamma tocopherol significantly reduced auricular thickness compared to control (57, −57, and −71%, respectively) and blank nanoemulsion (−50, −50, −67%, respectively). Relative to the suspensions of ASF, only the nanoemulsion of ASF containing gamma tocopherol significantly reduced auricular thickness (−60%), whereas the 40% reduction with nanoemulsions of delta tocopherol compared to suspension was not statistically significant. Auricular concentrations of cytokines TNF-alpha and IL-1 alpha were significantly reduced in mice treated only with ASF nanoemulsions of gamma tocopherol compared to control (−53, −46%, respectively) and blank nanoemulsion (−52, −46%, respectively). Auricular thickness was significantly associated with tissue TNF-alpha ( r = 0.539, p < 0.001) and IL-1 alpha concentrations ( r = 0.404, p = 0.01). Bioavailability for gamma and delta was dramatically enhanced (2.2- and 2.4-folds) with the nanoemulsion compared to suspensions. Only the plasma gamma tocopherol concentration was significantly associated with auricular thickness ( r = −0.643, P = 0.001). In conclusion, nanoemulsions of ASF containing gamma, alpha, and delta tocopherol, have enhanced anti-inflammatory properties and increased bioavailability, with gamma tocopherol, in particular compared to their suspensions.

Immune Response to Nocardia brasiliensis Extracellular Antigens in Patients with Mycetoma

The ability of culture-filtrate proteins to induce a cellular immune response in infected mice and humans was investigated. A crude extract culture filtrate of Nocardia brasiliensis (CFA) and five semi-purified CFA fractions (P1, P2, P3, P4, P5) were used to stimulate BALB/c mice spleen-cell cultures. The animals were divided into three groups: the first group was infected with 1 x 10(7) CFU of N. brasiliensis in the footpad, the second group was immunized with heat-killed bacteria, and the third was injected with sterile saline. IFN-gamma, IL-1alpha, and IL-4 concentrations were determined in culture supernatants. Protein fractions eliciting IFN-gamma production in mice, as well as the CFA, were used to stimulate IFN-gamma production and in vitro cell proliferation assays with peripheral blood mononuclear cells of patients with actinomycetoma by N. brasiliensis, individuals with pulmonary tuberculosis, and healthy controls. In mice, CFA and three of the protein fractions (P3, P4 and P5) induced significant IFN-gamma production in the infected group. In humans, only the CFA-induced IFN-gamma production and cell proliferation in the group of patients with actinomycetoma. There was no stimulation in tuberculosis patients nor healthy controls. These results suggest that some culture-filtrate antigens are recognized by patients with active actinomycetoma and do not cross-react with M. tuberculosis antigens, being therefore potential candidates to develop a diagnostic test.

Cytokine and chemokine levels in radicular and residual cyst fluids

Cytokines were thought to play an important role for the expansion of odontogenic cysts. The purpose of this study was to evaluate the cytokine and chemokine levels of radicular and residual cyst fluids. Cyst fluids were aspirated from 21 patients (11 radicular and 10 residual cysts) and the levels of interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were determined by ELISA using commercially available kits. Both radicular and residual cyst fluids contained IL-1alpha, TNF-alpha, MCP-1, and RANTES, concentrations of which were significantly higher in the radicular cyst fluids than those in the residual cysts (P < 0.001 for IL-1alpha, TNF-alpha, and RANTES; P < 0.01 for MCP-1). Compared to the other mediators, the concentration of IL-1alpha was found to be highest in both of the cyst fluids. In addition, positive correlations were found between IL-1alpha, TNF-alpha, MCP-1, and RANTES in radicular and residual cyst fluids. If the radicular cyst is inadvertently left behind following tooth extraction, some degree of inflammation may carry on. Residual cysts, although to a lesser extend than radicular cysts, have the potential to expand.

Characterization of the innate immune response to chronic aspiration in a novel rodent model

BackgroundAlthough chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung.MethodsGastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined.ResultsFollowing the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline.ConclusionThis represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.

Strain-Related Cytokine Profiles on the Murine Ocular Surface in Response to Desiccating Stress

To evaluate the effects of desiccating ocular surface stress on levels of inflammatory cytokines in the corneal epithelium, conjunctiva, and tear fluid of BALB/c and C57BL/6 mice. Experimental dry eye (EDE) was created in BALB/c and C57BL/6 mice by cholinergic blockade and exposure to a desiccating environment. Real-time polymerase chain reaction was performed to measure levels of cytokine transcripts. A multiplex immunobead assay was used to measure concentrations of these cytokines in tears. Experimental dryness significantly increased the expression of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor (TNF)-alpha transcripts in the corneal epithelium and conjunctiva of C57BL/6 mice. Strain-specific changes in tear cytokine profiles were observed. C57BL/6 mice had significantly greater tear concentrations of IL-1alpha and TNF-alpha and the Th-1 cytokines IL-2, IL-12, and interferon-gamma in response to desiccating stress than BALB/c mice. The Th-2 cytokines IL-4 and IL-10 were significantly greater in BALB/c tears. This study indicates that desiccating stress increases levels of certain cytokines in the corneal epithelium and conjunctiva in a strain-dependent fashion and that C57BL/6 mice had greater levels of Th-1 cytokines in their tears, whereas BALB/c mice had a greater increase in Th-2 cytokines.

Effect of interleukin-1alpha on the phagocytic function in cultured human trabecular meshwork cells

To investigate the effect of interleukin-1alpha (IL-1alpha) on the phagocytic function in cultured human trabecular meshwork (HTM) cells. HTM Cells were cultured and subcultured in vitro. The third to fifth passage of HTM cells were treated with different concentrations of IL-1alpha or vehicle in DMEM/F12 medium. 1000 of 0.85 microm microsphere/per cell were added to each well. The morphological changes of HTM cells were observed by an inverted phase-contrast microscope and electron microscope. The cellular phagocytic function of HTM cells was evaluated by counting the numbers of microsphere in 20 HTM cells using a light microscope. The break of HTM cell membrane was found under the electron microscope. The numbers of microsphere in HTM cells was significantly (P = 0.005) reduced in a dose- and incubation time-dependent manner (F = 3.603, P = 0.046, F = 15.846, P = 0.005, respectively). IL-1alpha affects the phagocytic function of HTM cells that is correlated to the concentration and the incubation time.

Decreased Proinflammatory Cytokines in Cervicovaginal Fluid, as Measured in Midgestation, are Associated with Preterm Delivery

The main aim of this study was to investigate the relationship between selected proinflammatory cytokines [interleukin IL-1 alpha (IL-1alpha), IL-1 beta (IL-1beta), IL-6 and IL-8] concentrations in cervicovaginal fluid, as measured in midgestation, and the risk of subsequent preterm delivery. Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22-34 weeks' gestation and analyzed for the concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 using enzyme-linked immunosorbent assay technique. Lower genital tract microbiology was diagnosed using Gram stain method and by culture. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 weeks (S.D. 4.7). Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between preterm and term delivery group. Women with lower genital tract pathological flora and IL-1alpha concentration below 25th percentile presented significant risk of subsequent preterm delivery as compared with women with no low cytokines (OR = 10.7; 95% CI, 2.0-58.1). Women with more than one cytokine' low concentration (below 25th percentile) presented an increased risk of preterm delivery--OR = 11.8 (95% CI, 1.8-78.0). The midgestation cytokines' measurement in cervicovaginal fluid of pregnant women could be useful for prediction of preterm delivery only among women with lower genital tract pathological flora.

Counter-Regulation of Interleukin-1α (IL-1α) and IL-1 Receptor Antagonist in Murine Keratinocytes

Interleukin-1alpha (IL-1alpha) is a potent proinflammatory cytokine constitutively expressed by keratinocytes, which also synthesize a specific inhibitor of IL-1 activity, intracellular IL-1 receptor antagonist (IL-1ra). Although homeostatic regulation of the IL-1 system in keratinocytes has long been suspected, there is currently little evidence for this. To explore this issue, the PAM212 murine keratinocyte cell line was exposed to increasing concentrations of either IL-1alpha or IL-1ra and the opposing ligand was assessed by ELISA. Release of IL-1ra was induced following stimulation by murine IL-1alpha in a concentration-dependent manner and, conversely, IL-1ra stimulation increased IL-1alpha release. To determine whether a similar homeostatic circuit operates in vivo, epidermis from transgenic mice in which overexpression of IL-1alpha or IL-1ra was targeted to keratinocytes was analyzed. Epidermal sheets derived from IL-1alpha transgenic mice released eight times more IL-1ra than those from wild-type mice following ex vivo culture and similarly, IL-1alpha release was increased 3-4-fold in epidermal sheets derived from IL-1ra transgenic epidermis, Use of specific neutralizing antibodies against type I and type II IL-1 receptors indicated that the counter-regulation mechanism is mediated extracellularly through the type I IL-1 receptor alone. Taken together, these observations provide the first demonstration of mutual counter-regulation of IL-1 receptor ligands in keratinocytes.

Interleukin‐1 levels in gingival crevicular fluid adjacent to restorations of calcium aluminate cement and resin composite

The aim of this clinical study was to intra-individually compare Class V restorations of a calcium aluminate cement (CAC), resin composite and enamel with respect to the adjacent levels of interleukin (IL)-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1ra) in gingival crevicular fluid (GCF). The hypothesis was that there are higher IL-1 levels adjacent to resin composite, compared with CAC and enamel. In 15 subjects, at least one set of two Class V restorations with subgingival margins, one CAC and one universal hybrid resin composite, and one control surface of enamel were included. In a cross-sectional study and on days 0, 3 and 7 of an experimental gingivitis study, GCFs were collected with Periopaper for 30 s. The GCF concentrations of IL-1alpha, IL-1beta and IL-1ra were quantified with enzyme linked immunosorbent assays. Neither the cross-sectional study nor the experimental gingivitis study showed any significant differences in the levels of IL-1alpha, IL-1beta and IL-1ra between CAC, resin composite and enamel sites (p>0.05). In the cross-sectional study, low IL-1 concentrations were observed. The IL-1 levels increased significantly during the experimental gingivitis. Regardless of CAC or resin composite, the restorations per se did not affect the GCF levels of IL-1 and IL-1ra, neither at healthy gingiva, nor at initiation of plaque-related gingival inflammation.

The Role of MIP-1? in Experimental Hypersensitivity Pneumonitis

S. rectivirgula (SR) causes Farmer's Lung Disease, a classic example of hypersensitivity pneumonitis (HP). We utilized a model of experimental hypersensitivity pneumonitis (EHP), antibody to MIP-1alpha and MIP-1alpha -/- mice, to test the hypothesis that MIP-1alpha is essential in the development of EHP. Treatment of C57BI/6 mice with anti-MIP-1alpha antibody did not change the extent of pulmonary histology abnormalities, BALF cell number or characteristics, or BALF concentration of IL12p40, TNF, IL1alpha and IL6, after an i.t. challenge with SR. MIP-1alpha -/- animals responded similarly to wild-type (wt) animals in the extent and nature of pulmonary histologic changes and BALF cell number and type after a single i.t. injection of SR There was a dose-response relationship between the amount of SR and BALF IL12p40, MCP-1 and IL6 in both strains, and MIP-1alpha in wild-type animals. We next transferred SR cultured spleen cells from SR sensitized mice (both wt and MIP-1alpha -/-) to naive recipients. Lung histology and BALF characteristics after SR i.t. challenge of the recipients were used to determine if adoptive transfer had occurred. Cultured cells from MIP-1alpha -/- animals were fully capable of transferring EHP to recipients. There was no difference of BALF TNF, IL6 and IL1alpha between the strains, but there was more MCP-1 and IL12p40 in the MIP-1alpha -/- mice than in the control mice. MIP-1alpha is not necessary for the recruitment of cells into the lung and BALF after i.t. administration of SR, or the development of cells able to adoptively transfer EHP.

Effects of scaling and root planing on the amounts of interleukin-1 and interleukin-1 receptor antagonist and the mRNA expression of interleukin-1beta in gingival crevicular fluid and gingival tissues.

The purpose of this study was to evaluate the relationship between the clinical changes after non-surgical periodontal therapy and interleukin 1 (IL-1) in gingival crevicular fluid (GCF) and gingival tissues from patients with chronic periodontitis. The inflammatory responses mediated by IL-1 play an important role in periodontal tissue destruction. Although numerous studies have attempted to elucidate the dynamic movement involved in chronic periodontitis, the results have often conflicted. Such discrepancies may have been due to the inability to determine clinical disease activity. Seven patients with chronic periodontitis were examined. The severity of periodontal inflammation was expressed using clinical parameters before and after a scaling and root planing (SRP) procedure. The amounts and concentrations of IL-1alpha, IL-1beta and IL-1 receptor antagonist in GCF were measured by enzyme-linked immunosorbent assay (ELISA) and IL-1 activity index was calculated. A needle biopsy in matching gingival tissues was also performed before and after the SRP procedure. The localization and mRNA expression of IL-1beta were determined using histological methods. Clinical parameters improved slightly after the SRP procedure. Only the probing pocket depth (PPD) was reduced significantly (p < 0.05). However, the amount of IL-1beta in GCF was slightly increased. The localization and mRNA expression of IL-1beta could still be observed after the SRP procedure. Therefore, none of the clinical parameters showed a high sensitivity or specificity for evaluating subgingival inflammation. These observations suggest that IL-1 is effective for evaluating in detail the state of subgingival inflammation.

Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.

To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP). Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA. An adult medical and surgical university hospital intensive care unit. Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls. None. Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL-1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively). Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.

Acid inhibitory potency of twice a day omeprazole is not affected by eradication of Helicobacter pylori in healthy volunteers.

The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. We undertook 24-hour pH-metry in 12 H. pylori-positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH >or= 3, as well as increasing the area under the H+ concentration-time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL-1alpha, IL-8, IL-13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H+ concentration-time curve 'without omeprazole' minus 'with omeprazole', when comparing 'after' versus 'before' eradication of H. pylori. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity 'with' versus 'without' omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.