hBD-2 Concentrations Research Articles

Associations between HBD3 and Pro-Inflammatory Cytokines in Asymptomatic Irreversible Pulpitis

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.

Implication of vitamin D-associated factors in patients with non-tuberculous mycobacterial lung disease.

Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.

Salivary antimicrobial defensins in pregnancy.

Susceptibility to and severity of gingival inflammation are enhanced during pregnancy; however, regulation of oral innate immune response, including antimicrobial peptides, during pregnancy is still unknown. We analysed salivary levels of human beta-defensin (hBD)-1, -2, -3, and human neutrophil peptide (HNP)-1 in pregnant women, and related those to their periodontal status. In this cohort study, 30 generally healthy, non-smoking Caucasian women without periodontitis were followed at three time points during pregnancy and twice post-partum. The non-pregnant group consisted of 24 women, who were examined three times at the following months. At each visit, periodontal status was recorded and stimulated saliva samples were collected. Salivary estradiol, progesterone, and defensin concentrations were measured by ELISA assays. After adjusting for visible plaque and gingival bleeding, reduced salivary concentrations of hBD-1, hBD-2, and HNP-1 were found especially during the third trimester, whereas hBD-3 concentrations did not change during pregnancy and post-partum visits. Weak associations were observed between salivary defensin and hormone concentrations and clinical parameters. There seems to be an independent regulation cascade for each antimicrobial defensin in the oral cavity during pregnancy, despite of the similarities between these antimicrobial peptides.

Vitamin D and L-Isoleucine Promote Antimicrobial Peptide hBD-2 Production in Peripheral Blood Mononuclear Cells from Elderly Individuals.

Elderly individuals are susceptible to develop infectious diseases; promoting innate immunity to prevent infections is a key issue. Human β-defensin-2 (hBD-2) is an antimicrobial peptide with antimicrobial and immunomodulatory properties. L-isoleucine and vitamin D are important molecules that induce hBD-2. The Aim of this study was to determine the use L-isoleucine and Vitamin D to induce hBD-2 in cells from healthy elderly individuals and elderly individuals with recurrent infections. We explored three groups: young adults (n = 20) used as control group, elderly adults (n = 18) and elderly with recurrent infections (n = 11). PBMCs (peripheral blood mononuclear cells) were isolated from the different groups and then were treated with L-isoleucine or vitamin D3. hBD-2 concentration was assessed with a sandwich enzyme Immunosorbent assay by triplicate. Using the vehicle as a mock control. Our results showed that a percentage of the individuals responded to the treatments producing hBD-2 (p < 0.05). These results showed that both molecules induced hBD-2 in elderly individuals and can be potentially used as prophylactic therapy to decrease infection diseases rates in this vulnerable group.

Vaginal Inflammation: Association between Leukocyte Concentration and Levels of Immune Mediators.

A wide variety of mediators are involved in inflammatory processes. However, the identity of those participating in vaginal immune responses has not been established. We correlated extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-8 (MMP-8), hyaluronan (HA), hyaluronidase-1 (Hyal-1), human β-defensin-2 (hBD2), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations with the extent of leukocyte infiltration into the vagina and suggest their participation in vaginal inflammation. Vaginal fluid was obtained from 233 women seen at the outpatient clinic in the Department of Obstetrics and Gynecology at Campinas University, Brazil. The magnitude of vaginal inflammation was determined by the leukocyte count on vaginal smears and categorized as no inflammation (0 leukocytes/field), moderate inflammation (1-4 leukocytes/field), and intense inflammation (>4 leukocytes/field). Concentrations of EMMPRIN, MMP-8, HA, Hyal-1, hBD2, and NGAL were determined in vaginal fluid by ELISA. EMMPRIN, MMP-8, HA, hBD2, and NGAL concentration increased with elevated leukocyte numbers (P<0.05), while Hyal-1 did not. EMMPRIN concentrations were correlated with HA and MMP-8 levels. EMMPRIN, MMP-8, HA, β-defensin, and NGAL are elevated in women with vaginal inflammation.

Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use. HIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception. Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log₁₀ ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log₁₀ ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar. Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.

Is variation in copy number of the human beta defensin gene cluster associated with preterm birth?

BackgroundIncreased expression of antimicrobial peptides including human beta defensins (HBD) has been reported in the amniotic fluid and vaginal secretions of women who deliver preterm. We have previously shown that these women have increased first trimester serum HBD2. The gene encoding HBD2, DEFB4A, is part of a defensin beta (DEFB) cluster on chromosome 8 that is variable in copy number. Increased serum HBD2 is associated with increased DEFB copy number. We aimed to test the hypothesis that variation in DEFB copy number is associated with preterm birth. MethodsIn a retrospective, case-control study, genomic DNA and serum were extracted from blood collected from white European women at 11–13 weeks' gestation attending King's College Hospital between March 1, 2006, and Sept 30, 2010. DEFB copy number was determined by paralogue ratio test. Serum HBD2 concentration was measured by ELISA. Data were analysed with Pearson correlation (Excel, version 2010) and binary logistic regression (SPSS, version 20). FindingsCases were 102 women who either delivered preterm in the index pregnancy or had a history of preterm delivery. Controls were 152 women who had had at least one previous term delivery and delivered at term in the index pregnancy; they had no history of preterm birth. Modal copy number was 4 (range 2–7). Serum was available from 140 women (30 cases, 54 controls, 56 not included in the genetic association study). Median HBD2 concentration was 761·5 pg/mL (IQR 449·6–1232·0). There was no association between DEFB copy number and preterm birth, nor was there a correlation between copy number and serum HBD2 concentration. InterpretationAlthough variation in HBD2 protein expression in the first trimester might be useful to predict risk of preterm birth, we found no association between DEFB copy number and preterm birth. Nor did we find a correlation between DEFB copy number and serum HBD2 expression in the first trimester of pregnancy; this might be due to variation in regulatory sequences—some of which are progesterone and oestrogen sensitive—between individual copies. FundingWellcome Trust, Wellbeing of Women.

Cathelicidin and human β-defensin 2 in bronchoalveolar lavage fluid of children with pulmonary tuberculosis.

The antimicrobial peptide cathelicidin LL-37/hCAP-18 and human β-defensins (hBD) are key factors in innate immune responses of the respiratory tract. To determine LL-37 and hBD-2 concentrations in the bronchoalveolar lavage (BAL) fluid of paediatric patients (aged <16 years) with pulmonary tuberculosis (TB) and to compare these with concentrations in healthy children. We measured peptide concentrations using an immunosorbent assay (ELISA). RESULTS Forty TB patients and 40 healthy controls were enrolled in the study (mean age 9.2 ± 4.7 and 8.3 ± 4.2 years, respectively, P = 0.97). The two groups exhibited no statistically significant difference in terms of sex, body mass index, relative weight or 25-hydroxyvitamin D levels. The mean BAL LL-37 level of the TB group was significantly higher than that of the control group (0.95 ± standard deviation [SD] 1.33 vs. 0.35 ± SD 0.51 ng/ml, P = 0.01, t = 2.54). The hBD-2 level was also higher in the TB group; however, the difference was not statistically significant (0.30 ± SD 0.58 vs. 0.14 ± SD 0.30 ng/ml, P = 0.11). There was no correlation between LL-37, hBD-2 and 25-hydroxyvitamin D levels. CONCLUSIONS Our data suggest that LL-37 and hBD-2 may play an important role in TB pathogenesis in children. To our knowledge, this is the first study on BAL LL-37 and hBD-2 concentrations in children with pulmonary TB.

8.4 Serum beta defensin concentration in the first trimester is related to genotype, and is higher in women who develop PPROM and deliver before 34 weeks

BackgroundPreviously we showed that the DEFB1 SNP rs1799946 is associated with PPROM and a four-fold increase in spontaneous preterm birth risk (PTB); rs1047031 may reduce the risk of PTB. This...

Role of defensins in the pathogenesis of chronic lung allograft rejection

Chronic rejection predominantly manifested as bronchiolitis obliterans syndrome (BOS), still remains a major problem affecting long-term outcomes in human lung transplantation (LTx). Donor specific antibodies (DSA) and infiltration of neutrophils in the graft have been associated with the development of BOS. This study determines the role of defensins, produced by neutrophils, and its interaction with α-1-antitrypsin (AAT) towards induction of airway inflammation and fibrosis which are characteristic hallmarks of BOS. Bronchoalveolar lavage (BAL) and serum from LTx recipients, BOS+ (n=28), BOS− (n=26) and normal healthy controls (n=24) were analyzed. Our results show that BOS+ LTx recipients had higher α-defensins (HNP1–3) and β-defensin2 HBD2 concentration in BAL and serum compared to BOS-DSA-recipients and normal controls (p=0.03). BOS+ patients had significantly lower serum AAT along with higher circulating concentration of HNP–AAT complexes in BAL (p=0.05). Stimulation of primary small airway epithelial cells (SAECs) with HNPs induced expression of HBD2, adhesion molecules (ICAM and VCAM), cytokines (IL-6, IL-1β, IL-13, IL-8 and MCP-1) and growth-factor (VEGF and EGF). In contrast, anti-inflammatory cytokine, IL-10 expression decreased 2-fold (p=0.002). HNPs mediated SAEC activation was completely abrogated by AAT. In conclusion, our results demonstrates that neutrophil secretory product, α-defensins, stimulate β-defensin production by SAECs causing upregulation of pro-inflammatory and pro-fibrotic signaling molecules. Hence, chronic stimulation of airway epithelial cells by defensins can lead to inflammation and fibrosis the central events in the development of BOS following LTx.

Progesterone Elicits an Inhibitory Effect upon LPS‐Induced Innate Immune Response in Pre‐Labor Human Amniotic Epithelium

Infection of human fetal membranes elicits secretion of pro-inflammatory modulators through its innate immune capacities. We investigated the effect of lipopolysacharide (LPS) and progesterone (P4) upon expression of TLR-4/MyD88, TNFα, IL-6, IL-8, IL-10, and HBD2 on the human amniotic epithelium. Explants of the human amniotic epithelium were pre-treated with 0.01, 0.1, and 1.0 μM of P4; then cotreated with 1000 ng/mL LPS. TLR-4 was immuno-detected, and concentrations of MyD88, TNFα, IL-6, IL-8, IL-10, and HBD2 were quantified by ELISA. P4 significantly reduced the expression of LPS-induced TLR-4/MyD88. LPS increased the concentrations of TNFα, IL-6, IL-8, IL-10, and HBD2 by factors of 30-, eight, three, three, and fivefold, respectively. P4 at 1.0 μM was the most effective dose to blunt the secretion of TNFα, IL-6, and HBD-2. RU-486 blocks the effect of P4. P4 inhibited LPS-induced TLR-4/MyD88 and pro-inflammatory factors in the human amniotic epithelium. These results could explain partially how P4 can protect the amniotic region of fetal membranes and generate a compensatory mechanism that limits the secretion of pro-inflammatory modulators, which could jeopardize the immune privilege during pregnancy.

Identification of sociodemographic and clinical factors associated with the levels of human β-defensin-1 and human β-defensin-2 in the human milk of Han Chinese

Human milk provides infants with various immune molecules. The objective of the present study was to measure human β-defensin-1 (hBD-1) and human β-defensin-2 (hBD-2) levels in the colostrum and mature milk of healthy Han Chinese, to identify factors regulating milk hBD-1 and hBD-2 expression and to explore the potential protective effect of milk hBD-1 and hBD-2 on infants. A total of 100 mothers and their babies were recruited into the study. Sociodemographic characteristics and other factors were obtained by a questionnaire. Babies were followed up for a period of 6 months. Colostrum samples (n 100) and mature milk samples (n 82) were collected by hand expression. The hBD-1 and hBD-2 concentrations were measured by ELISA. The hBD-1 and hBD-2 levels differed in the colostrum and mature milk. In the colostrum, the concentration ranges of hBD-1 and hBD-2 were 1·04-12·81 μg/ml and 0·31-19·12 ng/ml, respectively. In mature milk, the hBD-1 and hBD-2 levels were 1·03-31·76 ng/ml and 52·65-182·29 pg/ml, respectively. Several independent factors influence their production. The multivariable analysis showed a strong association between pre-pregnancy BMI and hBD-1 levels in the colostrum (P=0·001), mode of delivery was significantly associated with hBD-2 levels in the colostrum (P=0·006) and gestational age was significantly associated with hBD-1 levels in mature milk (P= 0·010). During the first 6 months of life, the incidence rate of upper respiratory infection was found to be less in the high-colostrum hBD-1 group than in the low-colostrum hBD-1 group (χ²=4·995, P=0·025). The present study suggested that the abundance of hBD-1 in the colostrum may have a protective function against upper respiratory infection for infants younger than 6 months.

Effects of yoga exercise on salivary beta-defensin 2

Yoga stretching can be done comfortably and easily by beginners and older adults to compensate for lack of exercise or poor health maintenance. The aim of this study was to determine the effect of yoga stretching on mucosal immune functions, primarily human β-defensin 2 (HBD-2) in saliva. Fifteen healthy adults (age, 60.4±8.0years) participated in the study. Participants rested for 90min on the first day and performed yoga for 90min on the second day. Measurements were carried out before and after rest or yoga. Saliva samples were collected by chewing a sterile cotton at a frequency of 60 cycles per min. Salivary HBD-2 concentration was measured using an enzyme-linked immunosorbent assay. HBD-2 concentration after yoga stretching (165.4±127.1pg/mL) was significantly higher than that before yoga stretching (84.1±63.4pg/mL; p<0.01). HBD-2 expression rate after yoga stretching (232.8±192.9pg/min) was significantly higher than that before yoga stretching (110.7±96.8pg/min; p<0.01). HBD-2 concentration (p<0.05) and HBD-2 expression rate (p<0.01) at post on the second day (yoga) was significantly higher than that on the first day (rest). POMS score of anger-hostility was lower after yoga than before. Yoga stretching for 90min can increase salivary HBD-2 expression in older adults. Therefore, yoga stretching might be useful for older adults and athletes to maintain their health.

Human β-Defensin 3 Peptide Is Increased and Redistributed in Crohn’s Ileitis

Antimicrobial peptides (AMPs) maintain a sterile environment in intestinal crypts, limiting microbial colonization and invasion. Decreased AMP expression is proposed to increase the risk for inflammatory bowel disease. Expression and function of inducible AMPs, human β-defensin 2 and 3 (hBD-2 and hBD-3), remain poorly characterized in healthy and chronically inflamed intestine. Peptide concentrations of hBD-2 and hBD-3 in serum and intestinal biopsies of subjects with ulcerative colitis and Crohn's disease (CD), and those of healthy subjects were measured by ELISA. Messenger RNA of hBD-2 and hBD-3 was quantified by quantitative PCR in biopsies from the terminal ileum (TI) of patients with CD and healthy controls. Peptide localization of hBD-3 in the TI was visualized by confocal microscopy. Immunoreactive hBD-3 peptide is present in the TI and colon in healthy subjects. In the TI of patients with CD, hBD-3, but not hBD-2 peptide, is increased 4-fold, whereas hBD-2 peptide is elevated in the serum. Messenger RNA of hBD-3 in the CD TI remains unchanged and does not correlate with hBD-3 peptide expression. However, hBD-3 is localized to Paneth cell granules and the apical surface of the healthy columnar epithelium. In CD, hBD-3 peptide location switches to the basolateral surface of the columnar epithelium and is diffusely distributed within the lamina propria. The peptide hBD-3 throughout the healthy gastrointestinal tract suggests a role in maintaining balance between host defenses and commensal microbiota. Increased and relocalized secretion of hBD-3 toward the lamina propria in the CD TI indicates possible local immunomodulation during chronic inflammation, whereas increased serum hBD-2 in CD implicates its systemic antimicrobial and immunomodulatory role.

Prognostic Value of Plasma Human β-Defensin 2 Level on Short-Term Clinical Outcomes in Patients With Community-Acquired Pneumonia: A Preliminary Study

Plasma level of human β-defensin 2 (HBD-2), noted to play a role in lung inflammatory diseases, is elevated in patients with pneumonia. To investigate the prognostic value of plasma HBD-2 concentration in predicting 30-day clinical outcomes in patients with community-acquired pneumonia (CAP). Patients with CAP were divided into 2 groups, based on the 30-day clinical outcomes, presence or absence of adverse outcomes (death, need for invasive mechanical ventilation, development of new complication of pneumonia). Demographic data, comorbidities, baseline clinical and laboratory features, plasma HBD-2 concentration, and the CURB-65 (confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 years of age) scores on admission were compared between the 2 groups in univariable analysis. Multivariable logistic regression was used to test the predictor of adverse outcomes. Receiver operating characteristic analyses were used to calculate the power of the assays to predict the 30-day adverse outcomes. We enrolled 361 subjects with CAP between March 2007 and March 2011. Univariate analysis revealed the following as predictive factors: age, smoking status, duration from symptom onset to admission, bilateral radiographic changes, total white-blood-cell count, serum sodium, serum potassium, serum albumin, plasma HBD-2 concentration, CURB-65 score, and comorbidities. In the multivariable logistic regression, plasma HBD-2 concentration, CURB-65 score, and age were independent predictors of 30-day adverse outcomes. In the receiver operating characteristic analysis, plasma HBD-2 concentration had an area under the curve of 0.77 (95% CI 0.71-0.82); the optimal cutoff point was 12.5 mg/L (sensitivity of 63%, specificity of 84%, positive predictive value of 42%, and negative predictive value of 88%), which predicted 30-day adverse outcomes in subjects with CAP. In CAP patients, plasma HBD-2 level on admission is associated with 30-day clinical outcomes, and lower plasma HBD-2 level is an independent predictor for adverse outcomes. Plasma HBD-2 level may become a useful tool for prognostic stratification in patients with CAP.

1375 Early Diagnostics of Necrotizing Enterocilitis in Newborn Infants Underwent Perinatal Asphyxia

Background and AimDefensins are antimicrobial peptides against gram positive and gram negative bacteria, fungus and viruses. The goal of the study is to reveal diagnostic fecal markers of necrotizing enterocolitis...

Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis

The aim of this study was to analyze whether the mucosal innate immune response of extremely-low-birth-weight (ELBW) infants might play a role in the development of necrotizing enterocolitis (NEC). Between April 2008 and December 2009 antimicrobial peptides were prospectively measured in fecal samples of ELBW infants. In cases requiring abdominal surgery, full-thickness gut biopsies were analyzed for expression of human β-defensin 2 (hBD2), interleukin-8 (IL-8), villin, MD2, and Toll-like receptor 4 (TLR4). Fecal hBD1 concentrations were consistently low in all patients, whereas hBD2 concentrations were high in meconium, particularly in clinical chorioamnionitis, and then dropped, followed by a steady increase after day 14. Infants with moderate NEC showed significantly increased fecal hBD2 concentrations before clinical symptoms, in contrast to infants developing severe NEC. Analysis of intestinal resection material obtained from patients with severe NEC revealed low hBD2 mRNA and protein levels, and increased expression of the inflammatory cytokine IL-8. High hBD2 concentrations, reflecting strong intestinal immune responses, were associated with moderate courses of the disease. In severe NEC, low hBD2 expression was accompanied by low TLR4/MD2 expression, suggesting an inadequate response to luminal bacteria, possibly predisposing those infants to the development of NEC.

Crenotherapy Modulates the Expression of Proinflammatory Cytokines and Immunoregulatory Peptides in Nasal Secretions of Children with Chronic Rhinosinusitis

The effect of crenotherapy on major mucosal markers of inflammation, TNF alpha, human beta-defensins 2 (hBD-2), and calprotectin, are largely unexplored in pediatric chronic rhinosinusitis (CRS). The aim of this study was to investigate the effects of crenotherapy with sulfate-sodium-chloride water on mucosal markers of inflammation in children with CRS. Children with CRS received 15-day crenotherapy consisting of sulfate-sodium-chloride thermal water inhalations by nasal aerosol (15 minutes/day). Concentrations of nasal mucosal markers of inflammation (TNF alpha, hBD-2, and calprotectin) were measured before and after crenotherapy. Presence of specific symptoms (nasal obstruction, nasal discharge, facial pain, sense of smell, and cough), value of symptoms score sino-nasal 5 (SN5), quality of life (QoL) score (1 [worse] to 10 [optimal]) were also assessed. After crenotherapy a significant reduction was observed in TNF alpha (from 0.14 ± 0.02 to 0.08 ± 0.01; p < 0.001), calprotectin (from 2.9 ± 1.0 to 1.9 ± 0.5; p < 9.001), and hBD-2 (from 2.0 ± 0.1 to 0.9 ± 0.6; p < 0.001) concentrations. A significant (p < 0.05) reduction in number of subjects presenting symptoms of nasal obstruction (100% versus 40%), nasal discharge (33% versus 13%), facial pain (30% versus 10%), and sense of smell (60% versus 20%) was observed. A significant improvement of SN5 (from 3.07 ± 0.76 to 2.08 ± 0.42; p < 0.001) was observed after the crenotherapy. QoL also improved after crenotherapy (from 4.2 ± 1.1 to 6.6 ± 1.0; p < 0.001). Crenotherapy induced a down-regulation of nasal mucosal inflammatory mediators in children with CRS.

Genetic polymorphisms of human β-defensins in patients with ischemic stroke

Genetic predisposition of the inflammatory host response may affect the development of stroke. On the basis of the theory of infectious burden and risk of stroke, we considered it of interest to investigate the relevance of the single-nucleotide polymorphisms (SNPs) in the DEFB1 gene and the copy number variant (CNV) of the DEFB4 genes in ischemic stroke. There were no significant differences in the genotype frequencies of the three SNPs of the DEFB1 gene between the patients with stroke (n = 312) and the healthy blood donors (n = 221). However, a higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with ischemic stroke as compared with the healthy controls (40% vs 24%, respectively). Additionally, low plasma concentrations of hBD-2 (187 ± 20 pg/ml) were characteristic of the patients with fewer than four copy numbers relative to those with more than four copy numbers (385 ± 35 pg/ml). The low copy number of the DEFB4 gene, involving a weakened antimicrobial defense of the host, might be important in the pathogenesis of stroke.

Multiple trauma induces serum production of host defence peptides

Today multiple trauma still is associated with a high mortality. Although severe open fractures and wounds can give rise to local infections and sepsis, the overall infection rate of multiply injured patients is surprisingly low. We have investigated serum of multiply injured patients with respect to antibacterial properties and screened for host defence peptides (HDP) that constitute a class of fast acting and rapidly available molecules preventing bacterial infection. Serum specimens were obtained from multiply injured patients. Radial diffusion assays were performed to investigate antimicrobial properties. Ultrafiltration and heat-inactivation were used to rule out antimicrobial activity of large proteins i.e. complement factors. ELISA was performed to analyse serum concentrations of the human beta-defensins 2 and 3 (hBD-2 and hBD-3), LL-37 and the proinflammatory cytokines interferon-gamma (IFN-γ) and interleukin-6 (IL-6). Serum of multiply injured patients showed greater zones of inhibition in antimicrobial testing against Gram negative und positive bacteria. This effect was mediated by proteins smaller than 10 kDa, inactivation of the complement system does not significantly reduce antibacterial action. hBD-2, hBD-3 and LL-37 concentrations were significantly elevated after trauma and followed different characteristic concentration curves. Similar patterns of concentration profiles were recorded for hBD-2/IL-6 and hBD-3/IFN-γ suggesting a stimulatory influence within their induction process. With this study we provide evidence, that serum of multiply injured patients has by far higher antibacterial capacity than that of healthy donors. As possible mediators we have detected the HDP hBD-2, hBD-3 and LL-37 and their inducers in serum of multiply injured patients.