Propolis extracts exhibit an immunoregulatory activity in an OVA-sensitized airway inflammatory animal model.
ABSTRACT Propolis, which has been used widely in folk medicine, has been shown to exhibit various biological activities but its immunoregulatory and anti-inflammatory activities in intact animals have not been well studied. We investigated these activities of propolis using an ovalbumin-induced asthma animal model. Mice were immunized and sensitized by exposure to ovalbumin (OVA) antigen and administered with low- (65 mg/kg body weight) and high-dose (325 mg/kg body weight) propolis water extracts by tube feeding. The serum OVA-specific IgE titer and cytokine profiles in cultured splenocytes and bronchoalveolar lavage fluids (BALF) were analyzed. The number of eosinophils in BALF was counted. Here we demonstrate that propolis extracts can suppress the serum levels of OVA-specific IgE and IgG(1), and airway hyperresponsiveness (AHR) in OVA-sensitized mice. There are no significant differences in the concentration of eotaxin or the number of eosinophils in BALF among the four groups. However, the higher dose of propolis extracts decreases the level of IL-5 in BALF. The splenocytes from mice administered with propolis extracts (low- and high-dose groups) exhibit a strong inhibition of IL-10 secretion and up-regulation of IFN-gamma secretion in splenocytes stimulated with concanavalin A (ConA). In addition, cytokine (IFN-gamma, IL-6, and IL-10) secretion in OVA-stimulated splenocytes from the propolis groups was significantly lower than that in the control group. These results suggest that propolis extracts may be a potential novel therapeutic agent for asthma.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: The dose of antigen is assumed to be one of the important factors in the polarized development of helper T cell subsets, i.e. Th1 or Th2 cells. We investigated the effect of the sensitizing antigen dose in a murine model of atopic asthma, which involved sensitization with ovalbumin (OVA) followed by repeated exposure to OVA aerosols. BALB/c mice were primed with varying doses of OVA (0, 10, 100 and 1000 microg) plus Al(OH)3 on days 0, 7 and 14, and were challenged with OVA aerosols (50 mg/ml for 20 min) on days 15-20. There were striking antigen dose-related differences in OVA-specific antibodies: high IgE and low IgG2a titres were found in mice sensitized at 10 microg, while low IgE and high IgG2a titres were seen at 1000 microg. The sensitizing dose was inversely correlated with the total cell count and the eosinophil count in bronchoalveolar lavage fluid (BALF), as well as with the extent of histological changes such as goblet cell hyperplasia of the bronchial epithelium and cellular infiltration into bronchovascular bundles. Antigen-induced bronchial hyper-responsiveness (BHR) to methacholine was observed with sensitization at 10 microg but not at 1000 microg. Splenic mononuclear cells (SMNC) obtained from mice sensitized at either dose showed proliferation in response to OVA. Production of IL-4 and IL-5 by OVA-stimulated SMNC was inversely correlated with the dose of sensitizing antigen. High-dose sensitization resulted in general suppression of cytokine production by SMNC, including interferon-gamma (IFN-gamma). The BALF levels of IL-4 and IL-5 were increased by low-dose sensitization, whereas IFN-gamma and IL-12 levels were increased by high-dose sensitization. These results suggest that the dose of sensitizing antigen defines the phenotypic changes in the present murine asthma model, presumably by influencing the pattern of cytokine production.Clinical & Experimental Immunology 11/1999; 118(1):9-15. · 3.41 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Knockout mice studies have revealed that NF-kappaB plays a critical role in Th2 cell differentiation and is therefore required for induction of allergic airway inflammation. However, the questions of whether NF-kappaB also plays a role in the effector phase of airway allergy and whether inhibiting NF-kappaB could have therapeutic value in the treatment of established asthma remain unanswered. To address these issues, we have assessed in OVA-sensitized wild-type mice the effects of selectively antagonizing NF-kappaB activity in the lungs during OVA challenge. Intratracheal administration of NF-kappaB decoy oligodeoxynucleotides to OVA-sensitized mice led to efficient nuclear transfection of airway immune cells, but not constitutive lung cells and draining lymph node cells, associated with abrogation of NF-kappaB activity in the airways upon OVA provocation. NF-kappaB inhibition was associated with strong attenuation of allergic lung inflammation, airway hyperresponsiveness, and local production of mucus, IL-5, IL-13, and eotaxin. IL-4 and OVA-specific IgE and IgG1 production was not reduced. This study demonstrates for the first time that activation of NF-kappaB in local immune cells is critically involved in the effector phase of allergic airway disease and that specific NF-kappaB inhibition in the lungs has therapeutic potential in the control of pulmonary allergy.The Journal of Immunology 12/2004; 173(9):5766-75. · 5.52 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: There is evidence that the cytokine IL-5 is a prominent feature of airway inflammation in asthma. The aim of this study was to determine whether exogenous IL-5 could cause changes in lung physiology, the early and late airway response after antigen challenge, and airway inflammation in rats that do not have a propensity to develop these changes after sensitization and challenge. Intratracheal administration of IL-5 to ovalbumin sensitized Brown Norway SSN rats increased the airway responsiveness to methacholine (AHR) 20 hours after administration of IL-5 at the same time as an increase in neutrophils occurred in the lung lavage. This effect was dose dependent and was not caused by endotoxin. Concurrent intratracheal administration of 50 ng of anti-IL-5 monoclonal antibody with 10 microg of recombinant human IL-5 decreased the AHR and neutrophil influx. Pretreatment with 3 microg of IL-5 had no effect on the early and late airway response or on AHR after ovalbumin challenge. However, IL-5 increased lung re-sistance 20 hours after antigen challenge. Although total lung cells and differential counts did not differ significantly 8 hours after antigen challenge, the blood lymphocyte CD4/CD8 ratio decreased in IL-5 pretreated rats (P <.05). In addition, in situ hybridization showed a significant increase in cells within the airway wall expressing IL-4 and IL-5 mRNA in IL-5 treated/challenged rats compared to controls (P <.05). The intratracheal administration of IL-5 causes only part of the physiologic changes that are associated with asthma. Other factors are necessary to obtain the complete asthma phenotype.Journal of Allergy and Clinical Immunology 03/2003; 111(3):558-66. · 12.05 Impact Factor