lactoferrin and Rhinitis--Allergic--Perennial

Neuronal involvement has been implicated in the pathophysiology of non-allergic and allergic rhinitis, contributing to the typical exacerbation of these conditions upon exposure to non-specific environmental irritants.. To determine if non-allergic and allergic rhinitis are characterized by increased responsiveness of the nasal mucosa to sensorineural stimulation.. Nasal challenges with capsaicin and its vehicle were performed in three groups of subjects -- non-allergic rhinitics, perennial allergic rhinitics, and healthy controls -- and resultant symptom scores, glandular secretion reflected by lactoferrin levels, and plasma extravasation reflected by albumin levels in nasal lavage fluid were compared.. Capsaicin-sensitive nerve stimulation produced increases in symptom scores and lactoferrin levels which were similar among the three groups of subjects. On the other hand, only the group of subjects with allergic rhinitis demonstrated a significant capsaicin-induced increase in albumin levels and a trend in total protein levels.. We conclude that non-allergic rhinitis is not characterized by increased responsiveness of capsaicin-sensitive nerve fibres; while allergic rhinitis is marked by hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This may reflect the activity of an axonal reflex to sensorineural stimulation.

Topics: Administration, Intranasal; Adult; Albumins; Allergens; Capsaicin; Cerebrospinal Fluid Rhinorrhea; Female; Fever; Humans; Lactoferrin; Male; Middle Aged; Nasal Mucosa; Neurons; Proteins; Rhinitis; Rhinitis, Allergic, Perennial; Tears

Lactoferrin (LF) can downregulate allergic airway inflammation in asthma. However, the in vivo effect of exogenous LF on allergic rhinitis (AR), a disease attributed to airway inflammation, has yet to be determined. We investigated the effect of intranasal administration recombinant human (rh) LF and its underlying mechanisms on AR in BALB/c mice. Multiple parameters of allergic responses were evaluated to determine the effect of rhLF. We found that the number of eosinophils and goblet cells, as well as mRNA and protein expression of type 2 helper T (Th2), Th17 and regulatory T (Treg) cells in the nasal cavity, was significantly upregulated in AR mice compared with the controls, Conversely, administration of rhLF prior to or after intranasal ovalbumin challenge markedly downregulated these same parameters. Th1-specific mRNA and protein expression in the nasal cavity of the controls was not different from that in AR mice, but expression significantly increased with rhLF treatment. The mRNA and protein expression of endogenous LF in the nasal cavity was significantly downregulated in AR mice compared with the controls. However, after rhLF treatment, endogenous LF mRNA and protein expression was significantly upregulated. Exogenous rhLF inhibited allergic inflammation in AR mice, most likely by promoting the endogenous LF expression and skewing T cells to a Th1, but not a Th2 and Th17 phenotype in the nasal mucosa. Our findings suggest that rhLF treatment may be a novel therapeutic approach for prevention and treatment AR.

Topics: Administration, Intranasal; Animals; Cytokines; Disease Models, Animal; Eosinophils; Goblet Cells; Inflammation; Lactoferrin; Lymphocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; RNA, Messenger; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells

Allergic rhinitis (AR) is a very common disease and a risk factor for allergic asthma. The discovery of new biomarkers for the early detection of AR would improve the clinical outcomes and reduce socio-economic burden. We sought to identify a novel serologic marker for detection of AR using a proteomic approach.. To identify the proteins involved in AR, comparative proteomics was applied using nasal lavage fluids (NLFs) taken before and after a nasal provocation test (NPT) with Dermatophagoides pteronyssinus (Dpt) in a subject with AR sensitized to Dpt. The clinical relevance of the identified proteins was evaluated by ELISA using NLFs and sera from the three study groups: Dpt-sensitive AR; asymptomatic Dpt-sensitive controls; and non-atopic healthy controls. The sensitivities and specificities of the candidate proteins for predicting AR were determined using receiver operating characteristic (ROC) curves.. In proteomic analysis, lactoferrin expression was up-regulated after NPT. The validation study using ELISA showed a significantly lower serum lactoferrin level in the AR group than those of the other two groups (P<0.05, respectively). To discriminate between subjects with or without AR, the optimal serum cut-off level of lactoferrin was set at <307 ng/mL using the ROC curve. The sensitivity and specificity for predicting AR were 81.4% and 58%. When combined with serum Dpt-specific IgE level, the sensitivity and specificity for predicting AR were 76.7% and 79.2%.. These results suggest that the serum lactoferrin level is associated with the phenotype of Dpt-sensitive AR, and in combination with the serum Dpt-specific IgE level, may be a potential serologic marker for early detection of AR.

Topics: Adult; Animals; Biomarkers; Dermatophagoides pteronyssinus; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin E; Lactoferrin; Male; Phenotype; Rhinitis, Allergic, Perennial; Sensitivity and Specificity; Skin Tests

The association of perennial allergic rhinitis (PAR) with recurrent sinusitis (RS) is well recognized. Anatomic abnormalities at the osteomeatal complex or ciliary dysfunction may play a significant role in some patients. However, for most patients with allergy, the determinants of RS are unknown.. To determine whether altered concentrations of antimicrobial peptides and proteins, such as lysozyme, lactoferrin, human beta-defensin-2 (HBD-2), and human neutrophil peptides 1 to 3 (HNP-1 to 3), contribute to the development of RS in patients with PAR.. Nasal secretions were collected by vacuum aspiration from 15 individuals with PAR+RS, 16 with PAR alone, and 16 controls. Lysozyme and lactoferrin levels were determined in nasal secretions by using quantitative enzyme-linked immunosorbent assay, and HBD-2 and HNP-1 to 3 levels were determined in nasal secretions by using semiquantitative Western blot analysis. Eosinophil-derived neurotoxin (EDN) levels were measured by using enzyme-linked immunosorbent assay as a marker of nasal eosinophilia in all 3 groups.. Levels of EDN were elevated significantly in patients with PAR+RS compared with controls. Lysozyme levels were decreased significantly in patients with PAR+RS compared with PAR alone or controls. Mean lysozyme levels were significantly lower in patients with EDN levels greater than 1,000 ng/mL vs those with levels of 1,000 ng/mL or less in the PAR+RS group. There were no statistically significant differences in lactoferrin, HBD-2, and HNP-1 to 3 levels among the 3 groups.. The presence of eosinophils and their products and reduced lysozyme concentrations may be critical factors that predispose the airways of patients with PAR to RS.

Topics: Adult; alpha-Defensins; beta-Defensins; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Eosinophil-Derived Neurotoxin; Eosinophilia; Female; Humans; Lactoferrin; Male; Muramidase; Nasal Lavage Fluid; Recurrence; Rhinitis, Allergic, Perennial; Ribonucleases; Sinusitis; Skin Tests

The aim of this study was to determine whether allergic inflammation induces nasal hyperreactivity to bradykinin by enhancing neuronal responsiveness.. We compared the response to localized, unilateral nasal challenge with bradykinin in patients with perennial allergic rhinitis and nonallergic subjects, and in patients with seasonal allergic rhinitis challenged in and out of season. Weights of secretions from each nostril were recorded, and levels of albumin and lactoferrin in secretions recovered from each nostril were assayed. Contralateral administration of atropine (0.32 mg) was used to evaluate the role of cholinergic reflexes in nasal hyperresponsiveness to bradykinin.. In patients with symptomatic allergy, bradykinin induced greater symptom scores than in asymptomatic atopic or nonallergic control subjects. Moreover, bradykinin caused sneezing in a majority of patients with symptomatic allergy but in none of the asymptomatic atopic or nonallergic control subjects. Only patients with symptomatic allergy showed dose-dependent bilateral increases in secretion weights and levels of the serous glandular marker, lactoferrin. In contrast, bradykinin induced similar increases in ipsilateral, but not contralateral, levels of albumin in all patient populations. Atropine inhibited contralateral secretion and lactoferrin production (p < 0.05) in patients with symptomatic allergy.. The induction of sneezing and of atropine-inhibitable contralateral glandular secretion demonstrates that allergic inflammation causes nasal hyperreactivity to bradykinin, at least in part, by enhancing neuronal responsiveness.

Topics: Adult; Albumins; Allergens; Atropine; Bradykinin; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Lactoferrin; Male; Muscarinic Antagonists; Nasal Mucosa; Nasal Provocation Tests; Reflex; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal