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PubMed2001

Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice.

BACKGROUND & AIMS: Integrins (alpha(4) and beta(2)) and their endothelial ligands vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) play key roles in leukocyte recruitment to areas of inflammation. ICAM-1 and VCAM-1 are expressed in inflamed intestinal tissues. This study investigates a possible causative role of adhesion molecules ICAM-1, VCAM-1, and alpha(4) integrins in mediating the inflammatory response in a murine model of Crohn's disease (CD). METHODS: CD4+ mesenteric lymph node cells from SAMP-1/Yit donor mice were adoptively transferred into major histocompatibility complex-matched severe combined immunodeficiency disease mice. Six weeks later, these mice were left untreated or treated for 3 days with monoclonal antibodies (mAbs) to ICAM-1, VCAM-1, or both, and alpha(4), or both ICAM-1 and alpha(4), dexamethasone, or nonblocking isotype control antibodies. On day 4 after treatment, tissues were investigated for expression of ICAM-1, VCAM-1, and for severity of inflammation using a semiquantitative inflammatory score. Dexamethasone treatment resolved all measures of intestinal inflammation. RESULTS: Blocking either ICAM-1, VCAM-1, or alpha(4) integrins had no significant beneficial effect. However, blocking ICAM-1 and alpha(4), or blocking ICAM-1 and VCAM-1, showed a 70% resolution of the active inflammation, but not chronic inflammation. CONCLUSIONS: These findings suggest that blocking ICAM-1 and VCAM-1 may have therapeutic benefit for the acute inflammatory component of Crohn's disease.

Adoptive Transfer↗
PubMed2002

Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice.

BACKGROUND & AIMS: Reduced gastric acid predisposes the stomach to colonization by bacteria and inflammation. Therefore, we investigated how the chronic gastritis in mice made hypochlorhydric by either gastrin deficiency or omeprazole treatment modulates epithelial cell function. METHODS: The gastric pathology of 16-week-old wild-type gastrin-expressing (G+/+) and gastrin-deficient (G-/-) mice maintained in conventional housing was compared. G-/- mice were then treated with antibiotics for 20 days. In a separate experiment, G+/+ mice were treated with omeprazole for 2 months or treated with omeprazole and antibiotics. RESULTS: Compared with the G+/+ animals, the hypochlorhydric G-/- mice showed significant inflammation that resolved after 20 days of antibiotic treatment and correlated with a decrease in bacterial overgrowth. Elevated G- and parietal-cell numbers in the G-/- mice, quantified by flow cytometry, normalized after antibiotic treatment. G+/+ mice treated with omeprazole had increased bacteria and mucosal lymphocytes that resolved after antibiotic therapy. Quantitation of the gastric cells in these omeprazole-treated mice revealed a significant increase in G- and parietal-cell numbers. On resolution of the gastritis, a decrease in parietal and gastrin-expressing (G) cells was observed despite sustained hypochlorhydria in the presence of omeprazole. CONCLUSIONS: Genetic or chemical hypochlorhydria predisposes the stomach to bacterial overgrowth resulting in inflammation. The specific changes in parietal and G cells correlate with the presence of inflammation and not directly with gastric acid. Thus, the normal stomach responds to inflammation by increasing the number and function of cell types that are able to maximize gastric acid output.

Achlorhydria↗
PubMed2006

Pathogenesis of bronchopulmonary dysplasia: the role of interleukin 1beta in the regulation of inflammation-mediated pulmonary retinoic acid pathways in transgenic mice.

BACKGROUND: Pulmonary inflammation, increased production of the inflammatory cytokine interleukin-1beta (IL-1beta), and vitamin A deficiency are risk factors for the development of bronchopulmonary dysplasia (BPD) in premature infants. To determine the mechanisms by which IL-1beta influences lung development, we have generated transgenic mice in which human IL-1beta is expressed in the lung epithelium with a doxycycline-inducible system controlled by the Clara cell secretory protein promoter. Perinatal IL-1beta production in these mice causes a phenotype that is strikingly similar to BPD. Pulmonary pathology in the mice shows inflammation, lack of alveolar septation, and impaired vascular development of the lung, similar to the histological characteristics of BPD. Retinoic acid (RA), one of the most biologically active derivatives of vitamin A, increases septation. Proteins involved in mediating the cellular responses to RA include the cellular retinoic acid binding proteins CRABP-I and CRABP-II and the nuclear retinoic acid receptors RAR-alpha, RAR-beta, and RAR-gamma. OBJECTIVE: To test the hypothesis that IL-1beta inhibits the expression of proteins involved in mediating the cellular response to RA. METHODS: The mRNA expression of CRABP-I, CRABP-II, RAR-alpha1, RAR-beta2, RAR-beta4, and RAR-gamma2 was studied with real-time RT-PCR on gestational day 18, and postnatal days 0, 1, 5, and 7 in IL-1beta-expressing mice and their control littermates. In addition, immunohistochemistry for CRABP-I was performed. RESULTS: IL-1beta decreased the mRNA expression and protein production of CRABP-I as well as the mRNA expression of RAR-gamma2. In contrast, no differences between IL-1beta-expressing and control mice were detected in the expression of CRABP-II, RAR-alpha1, RAR-beta2, or RAR-beta4. CONCLUSION: The present study demonstrates for the first time a link between inflammation and the retinoic acid pathway. Inhibition of CRABP-I and RAR-gamma2 expression may be one mechanism by which inflammation prevents alveolar septation. The therapeutic potential of RA in promoting septation in the setting of perinatal lung inflammation deserves further investigation.

Animals↗
PubMed2001

Electro-acupuncture attenuates behavioral hyperalgesia and selectively reduces spinal Fos protein expression in rats with persistent inflammation.

This study examined the effect of electro-acupuncture (EA) on persistent inflammatory hyperalgesia in a rat model. Inflammation and hyperalgesia were induced by injecting complete Freund's adjuvant (CFA) into one hindpaw of the rat. Hyperalgesia was determined by a decrease in paw withdrawal latencies (PWL) to a noxious thermal stimulus. EA was applied bilaterally at the acupuncture point Huantiao (G30) at the rat's hindlimbs. EA-treated rats (n = 11) had significantly longer PWLs as compared with placebo control rats (n = 7) in the inflamed paw at 2.5 hours and 5 days after injection of CFA (P <.05) and longer PWLs as compared to sham control rats (n = 9) at 2.5 hours (P >.05). Paw edema was significantly reduced in EA-treated rats versus placebo controls at 24 hours after inflammation (P <.01). Inflammation-induced spinal Fos expression in the medial half of laminae I-II in EA-treated rats versus placebo rats (n = 5 per group) was significantly reduced (P <.01). These data showed that EA delayed the onset and facilitated the recovery of inflammatory hyperalgesia and suppressed the inflammation-induced spinal Fos expression in neurons (laminae I-II) involved in receiving noxious stimulation. This rat model of persistent pain and inflammation seems to be an ideal animal model for studying the effect of acupuncture.

Journal Article↗
PubMed2001

The effect of varying frequency and intensity of transcutaneous electrical nerve stimulation on secondary mechanical hyperalgesia in an animal model of inflammation.

For years, transcutaneous electrical nerve stimulation (TENS) has been used clinically for the treatment of many types of pain. Although there have been many studies conducted on the efficacy of TENS in the clinical setting, the results are conflicting. The purpose of our investigation was to determine the effect of varying frequency and intensity of TENS on secondary mechanical hyperalgesia induced by acute joint inflammation. Male Sprague-Dawley rats were injected with a mixture of 3% carrageenan and 3% kaolin (100 microL in 0.9% sterile saline) into the joint cavity of one knee. The response threshold to mechanical stimuli was determined before inflammation of the knee joint; 4 hours after inflammation; immediately after the administration of TENS (approximately 5 hours after inflammation); and at 8, 12, and 24 hours after inflammation. TENS was applied to the inflamed knee joint at either high (100 Hz) or low (4 Hz) frequency and at either sensory or motor intensity. Sensory intensity was just below the threshold for motor contraction, and motor intensity was 2 x threshold for motor contraction. Either low- or high-frequency TENS is equally successful in reducing secondary mechanical hyperalgesia. Similarly, either sensory- or motor-intensity TENS equally reduces secondary mechanical hyperalgesia. Thus, selection of TENS should be based on patient comfort and symptoms for relief of secondary mechanical hyperalgesia.

Journal Article↗
PubMed2000

[Circumscribed choroidal granulomatous inflammation after perforating injury. A histopathological study of four eyes].

BACKGROUND: This study was performed to describe the clinicopathologic features of patients wo showed circumscribed choroidal granulomatous inflammation after trauma. METHODS: We examined histologically 4 eyes which had been enucleated within 4 weeks after treatment for perforating trauma. The second eyes of the patients were not affected. RESULTS: Four enucleated eyes with perforating injuries had focal uveal granulomatous inflammation of the posterior choroid. None of these eyes contained Dalen-Fuchs' nodules. One eye had a disrupted lens without lens-induced inflammation. All eyes exhibited choroidal ruptures. Foreign material could be detected in one of these eyes. CONCLUSIONS: Focal choroidal granulomatous inflammation may occur as a result of penetrating ocular trauma. The origin of this condition is unknown, although a foreign body reaction and choroidal rupture may be involved in the pathogenesis of the granulomatous inflammation.

Adult↗
PubMed2006

Effect of Oryza sativa extract on the progression of airway inflammation and remodeling in an experimental animal model of asthma.

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of smooth muscle and goblet cells, and subepithelial fibrosis. The present study was undertaken to evaluate the effects of DA-9201, an ethanolic extract of black rice (Oryza sativa L.), on airway inflammation and remodeling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 6 weeks. DA-9201 (30, 100, or 300 mg/kg) or dexamethasone (3 mg/kg) was orally administered during the last 4 and 2 weeks, respectively. Airway inflammation, lung pathology by histomorphometry and immunohistochemistry, IgE level and Th2 cytokines were evaluated. The OVA-treated mice showed extensive eosinophilia, chronic inflammatory responses and characteristics of airway remodeling including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. As compared to the OVA-treated control group, treatment with DA-9201 resulted in significant reductions in the accumulation of eosinophils in peribronchial areas, chronic pulmonary inflammation and progression of airway remodeling. Furthermore, DA-9201 significantly reduced total serum and BALF IgE levels and Th2 cytokines. These results indicate that DA-9201 may play an important role in attenuating the progressing of airway inflammation and remodeling and suggest the potential benefits of DA-9201 in prevention or treatment of asthma.

Animals↗
PubMed1991

[Usefulness of the Laser FLare Cell Meter (LFCM, Kowa FC-1000) for evaluating inflammation of the anterior chamber in clinical practice].

The Laser Flare Cell Meter (LFCM, Kowa FC-1000), an instrument measuring aqueous flare and cells in a quantitative, objective and non-invasive way, has been mainly used so far to measure inflammation in clinical and experimental research. In the light of some illustrative examples, its practical clinical usefulness is presented; the LFCM was found to be specially helpful in 3 types of situations. 1. In acute anterior uveitis (AAU) patients, precise LFCM monitoring of inflammation made it possible to avoid excessive corticosteroid therapy, mainly by more rapid and controlled tapering at the end of an inflammatory episode, so possibly minimizing steroid side effects in a group of patients prone to numerous uveitis recurrences. In a steroid-responder patient it allowed successful treatment of a flare-up of AAU with a combination of systemic and topical diclofenac (Voltaren), a potent nonsteroidal antiinflammatory drug. 2. LFCM monitoring of inflammation in patients undergoing laser treatments allowed optimal adjustment of antiinflammatory therapy. Diclofenac drops (Voltarene Ophta), were sufficient to treat inflammation in all patients, undergoing Nd-YAG laser posterior capsulotomy or Argon laser trabeculoplasty. 3. In patients with acyclovir treated herpes simplex or herpes zoster uveitis corticosteroid treatment should be avoided whenever possible, because of the tendency to develop steroid dependency. LFCM monitoring of this group of patients gave a precise evolutionary pattern of inflammation and permitted to avoid steroid treatment in many patients.

Acyclovir↗
PubMed2006

Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function.

In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by the administration of LPS in wild-type mice, whereas such increase was not observed in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from TLR4-deficient, mice restored the increased eosinophilic inflammation in mast-cell-deficient mice. Wild-type BMMCs pretreated with LPS in vitro also reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed that the treatment of BMMCs with LPS resulted in NF-kappaB activation, sustained up-regulation of GATA1 and -2 expression, and increased the capability to produce IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2 were detected in LPS-treated BMMCs after costimulation with LPS and IgE/Ag. Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of transcription of Th2 cytokines in BMMCs were decreased by the introduction of small interfering RNA for GATA1. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 and subsequent increase in Th2 cytokine production.

Adoptive Transfer↗
PubMed2001

A role for IL-1 alpha in inducing pathologic inflammation during bacterial infection.

Infection with pathogenic microbes often results in a significant inflammatory response. A cascade of proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and IL-1 initiates this response. Although there is a clear role for IL-1 during infection, little is known to distinguish the role of IL-1 alpha from that of IL-1 beta during this process. With the use of Yersinia enterocolitica as a model enteric pathogen, we have identified a specific role for IL-1 alpha in inducing pathologic inflammation during bacterial infection. Depletion of IL-1 alpha in mice infected with wild-type Y. enterocolitica results in significantly decreased intestinal inflammation. Furthermore, a bacterial mutant that does not induce IL-1 alpha expression but induces normal levels of IL-1 beta, TNF-alpha, and IFN-gamma, causes greatly reduced intestinal inflammation and is attenuated by LD(50) analysis in the C57BL/6 mouse model. These results demonstrate a distinct and unrecognized role for IL-1 alpha in inducing intestinal inflammation that cannot be compensated for by the endogenous levels of IL-1 beta, TNF-alpha, or IFN-gamma that are produced in response to Y. enterocolitica. Additionally, these results suggest that IL-1 alpha-induced inflammation is a major contributor to the pathology of yersiniosis.

Animals↗
PubMed2000

Interleukin-5-mediated allergic airway inflammation inhibits the human surfactant protein C promoter in transgenic mice.

Allergen challenge in the lung of humans and animals is associated with surfactant dysfunction, but the mechanism of this effect has not been established. By using a murine model of asthma we now report the effect of allergen-induced airway inflammation on the expression of transgenes regulated by the human surfactant protein (hSP)-C promoter. The hSP-C 3.7-kilobase pair promoter was used to direct the expression of eotaxin, an eosinophil-selective chemokine, into the lungs of several transgenic lines. As expected, the transgenic mice expressed increased amounts of eotaxin mRNA and protein compared with wild-type mice. Surprisingly, following allergen challenge, there was a marked down-regulation of transgene mRNA in three independent transgenic lines. The down-regulation was in contrast to other related proteins such as endogenous eotaxin and surfactant protein D levels, which were both increased following allergen challenge. Consistent with specific down-regulation of the eotaxin transgene, there was no increase in pulmonary eosinophil levels in the transgenic mice above that found in wild-type mice. Analysis of hSP-C transgenic mice with distinct reporter genes and 3'-untranslated regions revealed that allergen challenge was directly affecting the hSP-C promoter. We hypothesized that allergen-induced down-regulation of the hSP-C promoter was related to the eosinophilic inflammation. To test this, we blocked eosinophilic inflammation in the lungs by treating mice with neutralizing antiserum against interleukin-5. Interestingly, this treatment also blocked allergen-induced inhibition of the hSP-C promoter. These results establish that allergic airway inflammation is associated with up-regulation of the surfactant proteins primarily involved in immunity, whereas down-regulation of the surfactant protein primarily involved in maintaining airway patency. Furthermore, the marked down-regulation of the hSP-C promoter is interleukin-5-dependent, implying a critical role for eosinophilic inflammation. These results suggest that alterations in surfactant protein levels may contribute to immune and airway dysfunction in asthma.

3' Untranslated Regions↗
PubMed2001

Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway.

Agonistic antibodies against the Fas receptor, when administered to mice in vivo, cause significant apoptosis in the liver. In this study we show that anti-Fas antibody not only causes apoptosis of liver cells but also provokes hepatic inflammation. Two hours after injection of anti-Fas, when mice displayed evidence of caspase-3 activation and apoptosis, we found significant hepatic induction of the CXC chemokines macrophage inflammatory protein-2 and KC. Coincident with the chemokine induction was infiltration of the hepatic parenchyma by neutrophils. Neutralization experiments identified that chemokines were the cause of Fas-induced hepatic inflammation, with KC having the predominant effect. Chemokine induction in the livers of anti-Fas-treated mice was not associated with activation of NF-kappa B. Instead, it coincided with nuclear translocation of activator protein-1 (AP-1). AP-1 activation in liver was detected 1-2 h after anti-Fas treatment, suggesting a connection to the onset of apoptosis. When apoptosis was prevented by pretreating mice with a caspase-3 inhibitor, AP-1 activation and hepatic chemokine production were both significantly reduced. Hepatic inflammation was also reduced by 70%. Taken together, these findings indicate that Fas ligation can induce inflammation in the liver in vivo. Inflammation does not arise from Fas-mediated signaling through NF-kappa B; rather, it represents an indirect effect, requiring activation of caspase-3 and nuclear translocation of AP-1.

Animals↗
PubMed2002

Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation.

Initiation of lipid peroxidation and the formation of bioactive eicosanoids are pivotal processes in inflammation and atherosclerosis. Currently, lipoxygenases, cyclooxygenases, and cytochrome P450 monooxygenases are considered the primary enzymatic participants in these events. Myeloperoxidase (MPO), a heme protein secreted by activated leukocytes, generates reactive intermediates that promote lipid peroxidation in vitro. For example, MPO catalyzes oxidation of tyrosine and nitrite to form tyrosyl radical and nitrogen dioxide ((.)NO(2)), respectively, reactive intermediates capable of initiating oxidation of lipids in plasma. Neither the ability of MPO to initiate lipid peroxidation in vivo nor its role in generating bioactive eicosanoids during inflammation has been reported. Using a model of inflammation (peritonitis) with MPO knockout mice (MPO(-/-)), we examined the role for MPO in the formation of bioactive lipid oxidation products and promoting oxidant stress in vivo. Electrospray ionization tandem mass spectrometry was used to simultaneously quantify individual molecular species of hydroxy- and hydroperoxy-eicosatetraenoic acids (H(P)ETEs), F(2)-isoprostanes, hydroxy- and hydroperoxy-octadecadienoic acids (H(P)ODEs), and their precursors, arachidonic acid and linoleic acid. Peritonitis-triggered formation of F(2)-isoprostanes, a marker of oxidant stress in vivo, was reduced by 85% in the MPO(-/-) mice. Similarly, formation of all molecular species of H(P)ETEs and H(P)ODEs monitored were significantly reduced (by at least 50%) in the MPO(-/-) group during inflammation. Parallel analyses of peritoneal lavage proteins for protein dityrosine and nitrotyrosine, molecular markers for oxidative modification by tyrosyl radical and (.)NO(2), respectively, revealed marked reductions in the content of nitrotyrosine, but not dityrosine, in MPO(-/-) samples. Thus, MPO serves as a major enzymatic catalyst of lipid peroxidation at sites of inflammation. Moreover, MPO-dependent formation of (.)NO-derived oxidants, and not tyrosyl radical, appears to serve as a preferred pathway for initiating lipid peroxidation and promoting oxidant stress in vivo.

Catalysis↗
PubMed2001

IL-1beta, IL-1Ra and sIL-1RII in the culture supernatants of PMN and PBMC and the serum levels in patients with inflammation and patients with cancer disease of the same location.

An inflammation or an other malignant process may create a microenvironment that modulates the production and activity of cytokines and their regulators. In the present study we compared the secretion of IL-1beta and its regulatory proteins: IL-IRa and sIL-1RII by PMN and PBMC derived from patients with inflammation and patients with cancer disease of the same location. We also examined the serum levels of these mediators in groups of patients. The results obtained revealed changes in the secretion of IL-1beta and IL-1Ra which are more characteristic of PMN and PBMC from cancer patients than of the cells from patients with inflammation. In contrast, the secretion of sIL-1RII is more characteristic of PMN and PBMC derived from patients with inflammation. Furthermore, PMN appear to play more significant role in the secretion of IL-1Ra into the circulation of cancer patients than PBMC. In contrast, PBMC affect to a large extent the secretion of IL-1beta and sIL-1RII into the circulation of patients with inflammation than PMN. Concluding, the secretion of IL-1beta and its regulatory proteins may depend on the type of immune cells and the type of the disease.

Adult↗
PubMed1998

Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals.

Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rare. Additionally, ultrafine (uf) forms of these metals are used increasingly and there is little available information on their toxicity. Thus the inflammatory response following intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and sustained inflammation, cytotoxicity and increased epithelial permeability. The next most toxic material was DQ12 quartz, with Uf-Co being closely similar in ability to cause inflammation. Uf-TiO2 was more active than the saline control in all of the indices, but was the least toxic of the particles studied. The present study reveals that three ultrafine particles of the same diameter are dramatically different in their ability to cause inflammation. The three ultrafines were compared as to their ability to cause free-radical damage to supercoiled plasmid DNA, and the result of free-radical activity was found to be Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle types.

Animals↗
PubMed1999

Urban air particulate inhalation alters pulmonary function and induces pulmonary inflammation in a rodent model of chronic bronchitis.

Epidemiological studies have reported increased morbidity in human populations following inhalation of elevated levels of urban particulate matter. These responses are especially prevalent in populations with chronic obstructive pulmonary diseases, including chronic bronchitis. Toxicological studies have reported altered pulmonary function and increased pulmonary inflammation following particulate inhalation in the laboratory setting. However, most of these studies have utilized artificial particles that may not accurately mimic outdoor air pollutant conditions. Few studies have utilized actual urban air particle samples in inhalation studies. In the present study, the effects of inhaled concentrated urban air particulates on pulmonary function and pulmonary inflammation are addressed. Normal rats and rats with chronic bronchitis induced by approximately 200 ppm SO(2) for 6 wk were subsequently subjected to filtered air or concentrated air particles (CAPs). Twelve rats per group in 4 groups (48 rats total) were exposed for 5 h/day for 3 consecutive days. The CAPs aerosol levels were 206, 733, and 607 microg/m(3) (MMAD = 0.18 microm, sigma(g) = 2.9) on days 1, 2, and 3, respectively. Following the final day of exposure, pulmonary function parameters, including peak expiratory flow (PEF), tidal volume (TV), respiratory frequency (RF), and minute volume (MV), were measured and compared to preexposure baseline levels. Twenty-four hours following the final day of exposure, bronchoalveolar lavage was performed for total cell counts, differential cell counts, and total lavage protein levels. Pulmonary responses to CAPs in chronic bronchitic animals indicated a significant increase in tidal volume as well as peak expiratory flow. In CAPs-exposed animals without underlying bronchitis, significantly increased tidal volume was observed. Significant pulmonary inflammation was observed in the CAPs-exposed animals, particularly those with chronic bronchitis. Significant increases in neutrophils, lymphocytes, and total lavage protein were observed. These results suggest two distinct mechanistic responses to inhaled particles: a stress-type pulmonary function response marked by increases in flow and volume, that is, deeper breathing; and acute pulmonary inflammation marked by cellular influx, particularly neutrophils. From these data it is concluded that inhaled urban air particles alter pulmonary breathing parameters and increase pulmonary inflammation.

Air Pollutants↗
PubMed2001

Acute effect of inhaled budesonide on bronchial inflammation in asthmatic rats.

Although anti-inflammatory potency of inhaled corticosteroids is well established, little is known about their role in the acute phase. The aim of this study was to compare the acute anti-inflammatory effect of inhaled budesonide with systemic dexamethasone on allergen-induced inflammatory changes in asthmatic rats. Eighty-four Sprague Dawley rats were divided into four groups; group I (control, n = 24), group II (ovalbumin sensitized, n = 24), group III (systemic dexamethasone, n = 24), and group IV (budesonide, n = 12). All groups except group I were given ovalbumin aerosol challenges 14 days after sensitization with ovalbumin. The same procedure was applied to the control group using 0.9% saline. Group III received dexamethasone 0.3 mg/kg intraperitoneally and group IV received inhaled budesonide 10mL (0.5mg/mL) twice before the challenge. Eight hours after the challenge, bronchi of all the rats were evaluated for the degree of peribronchial inflammation. The most severe inflammation was seen in 8 of 24 rats (33%) in the second group, in 1 of 24 rats (4%) in the third group, and in 1 of 24 rats (4%) in the control group. None of the rats in group IV showed severe inflammation. No statistically significant difference was detected with respect to the presence of 3+ inflammation between the control vs. dexamethasone-, control vs. budesonide-, and dexamethasone vs. budesonide-receiving groups. Budesonide administration via nebulizer prior to exposure to an allergen may attenuate bronchial inflammation as effectively as systemic dexamethasone in rats.

Acute Disease↗
PubMed2003

Correlation of exhaled nitric oxide levels and airway inflammation markers in stable asthmatic patients.

Monitoring of inflammation is an important factor in asthma management. The gold standard for measuring direct airway inflammation is bronchial biopsy specimens taken from proximal airways through a fiberoptic bronchoscope. As a noninvasive procedure, the use of exhaled nitric oxide (FENO) for monitoring airway inflammation has been reported in many studies. The aim of this study was to evaluate the correlation of FENO with direct measurements of airway inflammation in biopsy specimens and pulmonary function tests (PFT). Histopathologic features were observed on bronchial biopsy specimens obtained from nine stable mild-moderate asthmatics. Each subject had measurements of PFT, FENO levels, blood eosinophil count, and bronchoscopy with bronchial biopsies and bronchoalveolar lavage. Five subjects with forced expiratory volume in 1 second >80% had methacholine challenge test. None of the subjects had prior anti-inflammatory therapy for asthma. No correlation was found between PFT, blood eosinophil count, and FENO levels. There was a negative correlation between PC20 and FENO. Though there was no correlation between bronchial biopsy eosinophil, monocyte and lymphocyte counts, and FENO, we found a weak positive correlation between total inflammatory cell count in bronchial biopsies and FENO levels. A negative significant correlation was found between FENO levels and epithelial desquamation (p<0.05, r=-0.7). These results suggest that, FENO levels reflect the increased number of activated inflammatory cells in airways and the negative correlation with epithelial desquamation reflects the role of epithelium in NO syntheses. FENO should not be interpreted as a specific inflammation marker for asthma.

Adult↗