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PubMed1994

Joint inflammation is reduced by dorsal rhizotomy and not by sympathectomy or spinal cord transection.

OBJECTIVES: To investigate the role of primary afferents, sympathetic postganglionic efferents and descending systems on the central control of peripheral inflammation. METHODS: Acute inflammation was induced by intra-articular injection of kaolin and carrageenan into the knee joint cavity of the rat. Before the induction of the arthritis, a unilateral dorsal rhizotomy, a chemical (phentolamine) and/or surgical sympathectomy, or a spinal transection was performed. Joint inflammation (joint circumference and thermographic readings) and behavioural signs were assessed. RESULTS: Only arthritic animals with a dorsal rhizotomy showed a significant reduction of the inflammatory response compared with control arthritic animals. No significant differences in the inflammatory response occurred following sympathectomy or spinal transection. The animals who received sympathectomy showed similar behavioural manifestations to the arthritic animals. CONCLUSIONS: The central terminals of primary afferents are important in the development of acute joint inflammation since dorsal rhizotomy attenuated the inflammatory response in the knee joint. The sympathetic nervous system is not involved in the acute inflammatory phase of this arthritis model. The central processes controlling acute inflammation involve a local spinal circuit since spinal cord transection at T9 has no effect on the inflammation.

Acute Disease↗
PubMed1991

Value of positive technetium-99m leucocyte scans in predicting intestinal inflammation.

The value of positive scans of autologous 99mTc-labelled leucocytes in the detection of intestinal inflammation was assessed in 29 patients with known inflammatory bowel disease and a high probability of intestinal inflammation and 58 with a low probability of intestinal inflammation comprising 37 with intestinal symptoms and 21 with suspected abscess. Autologous leucocytes were labelled with 99mTc using either of the established methods. In patients with inflammatory bowel disease, 3/13 with ileocaecal and 1/11 with colonic accumulation of 99mTc were incorrectly diagnosed in that there was no histological evidence of inflammation in those regions. In the low probability patients, all 26 positive images were false positives: there were 19 in the ileocaecal and 7 in colonic regions and no differences between the two subgroups. False positives were more common in low probability than high probability patients (p = 0.011). The results were independent of the 99mTc cell labelling technique used. Three false positive patients also had normal scans for 111In-labelled granulocytes. The time of first detection of 99mTc in the bowel was earlier in true than in false positive patients (92% v 33% within 1 h, p = 0.008), the false positive rates in the first hour of imaging being 5% in high and 15% in low probability patients. In 99mTc scintigraphy, the appearance of the isotope in the intestine occurs commonly in the absence of inflammation irrespective of the cell labelling technique used. In high probability patients, imaging at 1 h can more reliably discriminate true from false positives and retain clinical usefulness. In low probability patients specificity remains unacceptable and 99mTc-labelled leucocyte scanning in these patients is of little value as a positive predictor of intestinal inflammation.

Adolescent↗
PubMed1990

Inflammation in the lungs of rats after deposition of dust collected from the air of wool mills: the role of epithelial injury and complement activation.

In a previous study assessing respiratory symptoms in individuals employed in wool textile mills in the north of England relations between symptoms of chronic bronchitis, breathlessness and wheeze, and rhinitis and current exposure to airborne mass concentration of dust were shown. As preliminary steps in defining the potential hazard associated with dust from the air of wool mills the ability of inspirable dust, collected from the air of wool textile mills, to cause inflammation when injected into the lungs of rats was determined. Dusts were collected from the beginning of wool processing (opening) in one factory and from the middle (combing) and late (backwinding) stages of the process in two other factories. Ability of the dusts to cause inflammation was assessed by instillation into the lungs of rats followed by bronchoalveolar lavage. All the dusts caused some inflammation which peaked on day 1 and did not persist beyond one week. A distinctive aggregation response of mononuclear cells in the lavage, however, had a different time course, peaking at day 7. An attempt was made to determine how the wool mill dusts caused inflammation and experiments showed that the dusts themselves had no inherent chemotactic activity but that they did have a pronounced ability to generate chemotaxins in serum and so could activate complement in lung fluid. In addition, dust collected from ledges in the mills had the ability to injure epithelial cells in vitro which could also contribute to inflammation. A role for endotoxin in the inflammatory activity of the dusts was not discounted and a leachate of the dust had the ability to cause inflammation when injected into the lungs of rats. Wool mill dust is likely to be a complex mixture of materials and these experiments represent a preliminary approach to understanding the biological activity of the whole unfractionated dust and further studies are in progress to define more accurately the toxic material(s) in the dust.

Animals↗
PubMed2005

Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation.

BACKGROUND: Lung disease in cystic fibrosis (CF) is established in early childhood with recurrent bacterial infections and inflammation. Using spirometry, the effect of this early lung damage cannot be measured until a child is 6 years of age when some irreversible lung damage may already have occurred. Techniques for measurement of lung function in infants and young children include raised volume rapid thoracic compression (RVRTC) and low frequency forced oscillation (LFFOT). The aim of this study was to investigate the role of inflammation and infection on a population of infants and young children with CF and to determine whether lung function in this population (measured by LFFOT) is affected by early lung disease. METHODS: Lung function was measured by LFFOT in 24 children undergoing bronchoalveolar lavage (BAL) on 27 occasions as part of an annual programme while still under general anaesthesia. Following lung function testing, three aliquots of saline were instilled into the right middle or lower lobe. The first aliquot retrieved was processed for the detection of microbes, and the remaining aliquots were pooled to assess inflammatory markers (cytology, IL-8, NE, LTB(4)). RESULTS: Inflammation (percentage and number of neutrophils) was significantly higher in children with infections (p<0.001, p = 0.04, respectively), but not in those with symptoms. Several markers of inflammation significantly correlated with LFFOT parameters (R, G, and eta). CONCLUSION: Infections and inflammation are established before symptoms are apparent. Inflammation is correlated with measures of parenchymal changes in lung function measured by LFFOT.

Airway Resistance↗
PubMed1999

IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation.

Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 -/- mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 -/- mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 -/- mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 -/- mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.

Animals↗
PubMed2002

Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs.

Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.

Acute-Phase Reaction↗
PubMed2000

Adenoviral E3-14.7K protein in LPS-induced lung inflammation.

The adenoviral E3-14.7K protein is a cytoplasmic protein synthesized after adenoviral infection. To assess the contribution of E3-14. 7K-sensitive pathways in the modulation of inflammation by the respiratory epithelium, inflammatory responses to intratracheal lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha were assessed in transgenic mice bearing the adenoviral E3-14.7K gene under the direction of the surfactant protein (SP) C promoter. When E3-14.7K transgenic mice were administered LPS intratracheally, lung inflammation as indicated by macrophage and neutrophil accumulation in bronchoalveolar lavage fluid was decreased compared with wild-type control mice. Lung inflammation and epithelial cell injury were decreased in E3-14.7K mice 24 and 48 h after LPS administration. Intracellular staining for surfactant proprotein (proSP) B, proSP-C, and SP-B was decreased and extracellular staining was markedly increased in wild-type mice after LPS administration, consistent with LPS-induced lung injury. In contrast, intense intracellular staining of proSP-B, proSP-C, and SP-B persisted in type II cells of E3-14.7K mice, whereas extracellular staining of proSP-B and proSP-C was absent. Inhibitory effects of intratracheal LPS on SP-C mRNA were ameliorated by expression of the E3-14.7K gene. Similar to the response to LPS, lung inflammation after intratracheal administration of TNF-alpha was decreased in E3-14.7K transgenic mice. Levels of TNF-alpha after LPS administration were similar in wild-type and E3-14.7K-bearing mice. Cell-selective expression of E3-14.7K in the respiratory epithelium inhibited LPS- and TNF-alpha-mediated lung inflammation, demonstrating the critical role of respiratory epithelial cells in LPS- and TNF-alpha-induced lung inflammation.

Adenovirus E3 Proteins↗
PubMed1988

Enhancement of pulmonary inflammation by PGE2: evidence for a vasodilator effect.

We explored the potential proinflammatory effect of prostaglandins of the E series (PGE's) in a rabbit model of acute pulmonary inflammation. The instillation of fragments of the fifth component of complement (C5f) into the lung resulted in a localized area of inflammation, the extent of which was quantified by the total number of neutrophils and protein recoverable by bronchoalveolar lavage (BAL). Utilizing 111In-labeled neutrophils and serial scintigraphy, neutrophil localization in the area of inflammation was detected as early as 20 min after C5f instillation and reached a maximum between 2 and 4 h. The simultaneous intrabronchial administration of 100 micrograms of PGE2 resulted in a twofold increase in the accumulation of neutrophils in the area of inflammation as determined scintigraphically, a fivefold increase in BAL neutrophils, and a threefold increase in BAL protein. A proinflammatory effect on lavage constituents was also seen with the intravenous administration of PGE2 (100 ng.kg-1.min-1) and PGE1 (50 ng.kg-1.min-1) as well as in animals pretreated with a PGH synthase inhibitor, meclofenamate, and a thromboxane synthase inhibitor, dazmegrel. The effect of intrabronchial PGE2 to potentiate the inflammatory response was attenuated by the intravenous administration of a vasoconstrictor (angiotensin II) and mimicked by a vasodilator (nitroprusside), suggesting an effect of vasodilation per se. Using radiolabeled microspheres, it was determined that in response to the C5f alone, there was a 50% decrease in local blood flow to the area of inflammation, a pattern different from that seen in the systemic circulation. This decrease was prevented by the concomitant administration of PGE2 or nitroprusside. We conclude that vasodilation induced by PGE2 is associated with enhancement of pulmonary inflammation.

Animals↗
PubMed1989

Inhibition of neutral endopeptidase potentiates neurogenic inflammation in the rat trachea.

The present study was performed to determine whether neurogenic inflammation in the rat trachea can be exaggerated by inhibiting neutral endopeptidase, an enzyme that degrades tachykinins that are believed to mediate neurogenic inflammation. Neurogenic inflammation was produced by antidromic electrical stimulation of one vagus nerve (2.5 Hz, 1 ms, 5 V for 5 min) in the presence of atropine or by an intravenous injection of capsaicin (100 micrograms/kg). Neutrophils that adhered to the endothelium of venules were visualized and counted in tracheal whole mounts that were stained by a histochemical reaction for myeloperoxidase. Neural inflammation increased the number of adherent neutrophils. Pretreatment with the neutral endopeptidase inhibitor phosphoramidon (1.0 or 2.5 mg/kg iv) increased neutrophil adhesion induced by neural inflammation. As assessed by the amount of extravasation of Monastral blue pigment, neural inflammation also increased vascular permeability, and this change was potentiated by phosphoramidon. These results are consistent with the concept that neuropeptides released from sensory nerves in the tracheal mucosa cause neutrophils to adhere to venules and increase vascular permeability and that these effects are modulated by neutral endopeptidase.

Animals↗
PubMed1991

Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane.

The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response.

Animals↗
PubMed1999

Ozone-induced pulmonary inflammation and epithelial proliferation are partially mediated by PAF.

Ozone (O3) exposure stimulates airway inflammation and epithelial sloughing in a number of species, including mice. Platelet-activating factor (PAF) is a lipid mediator released by activated mast cells, macrophages, and epithelial cells and causes pulmonary inflammation and hyperpermeability. We hypothesized that the activation of PAF receptors is central to the development of inflammation and epithelial injury induced by acute O3 exposure in mice. To test this hypothesis, O3-susceptible C57BL/6J mice were treated with a PAF-receptor antagonist, UK-74505, or vehicle either before or immediately after 3-h exposure to O3 (2 parts/million) or filtered air. Bronchoalveolar lavage (BAL) fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage were used as indicators of inflammation in the airways. O3-induced epithelial injury was assessed by light microscopy, and DNA synthesis in epithelium of terminal bronchioles was estimated by using a bromodeoxyuridine-labeling index. Intercellular adhesion molecule 1 (ICAM-1) expression was also examined in the lung by immunohistochemical localization. O3 caused significant increases in polymorphonuclear leukocytes and protein in the BAL fluid, increased pulmonary epithelial proliferation, and increased epithelial expression of ICAM-1 compared with air-exposed, vehicle-treated control mice. Relative to O3-exposed, vehicle-treated control mice, UK-74505 before exposure significantly (P < 0.05) decreased BAL protein, polymorphonuclear leukocytes, and epithelial cells. O3-induced inflammation was similarly attenuated in mice treated with UK-74505 after exposure. These experiments thus support the hypothesis that O3-induced airways inflammation and epithelial damage in mice are partially mediated by activation of PAF receptors, possibly through modulation of ICAM-1 expression.

Animals↗
PubMed2004

Granulocyte extravasation and recruitment to sites of interstitial inflammation in patients with renal failure.

BACKGROUND: We have shown that leukocytes collected from sites of interstitial inflammation in patients on hemodialysis have a disturbed expression of CD11b compared to cells from healthy subjects. The aim of the present study was to study adhesion molecule expression on granulocytes in the peripheral circulation and at sites of interstitial inflammation in patients with renal failure. METHODS: Two skin blisters were raised in 10 patients and 19 healthy subjects and interstitial exudates collected (0 h). Skin chambers were applied and exposed to buffer or serum for 10 h in order to induce an intermediate and an intense interstitial inflammation. Cells and blister fluid were collected for determination of leukocyte count, CD11b/CD62L expression, interleukin-8 (IL-8) concentration in the interstitium and blister activity in terms of CD11b up-regulation. RESULTS: At the sites of intermediate and intense inflammation, granulocytes from patients with renal failure showed significantly higher expression of CD62L (p < 0.01 and p < 0.001, respectively) and significantly lower expression of CD11b (p < 0.0001 and p < 0.0001, respectively) compared to corresponding cells from healthy subjects. The interstitial concentration of IL-8 was significantly lower at the sites of intermediate (p < 0.005) and intense inflammation (p < 0.05) in patients with renal failure compared to in healthy subjects. In order to explore whether the decreased CD11b expression observed in patients is due to the interstitial milieu, blister exudates from patients and healthy subjects were incubated with leukocytes from healthy blood donors. Blister exudates from patients had a similar capacity to mobilize CD11b on granulocytes in vitro compared with blister exudates from healthy subjects. There was no consistent correlation between the expression of adhesion molecules on granulocytes in the interstitium and the concentration of IL-8 or the total interstitial concentration of chemotactic mediators. CONCLUSION: Constitutive cellular determinants are probably involved in the disturbed expression of adhesion molecules on granulocytes at sites of interstitial inflammation in patients with renal failure.

Adult↗
PubMed2005

Production of salivary immunoglobulin A and suppression of Dermatophagoides pteronyssinus-induced airway inflammation by local nasal immunotherapy.

BACKGROUND: Local nasal immunotherapy (LNIT) is an effective immunotherapeutic modality, especially when targeting a single immunodominant peptide from an allergen. However, the working mechanisms of LNIT are poorly understood. We hypothesized that LNIT with a mixture of group 2 allergens of Dermatophagoides pteronyssinus (Der p 2) protein and fungal immunomodulatory peptide (FIP) would generate suppression of Der p-induced airway inflammation through immunoglobulin (Ig) A secretion in the airways. METHOD: Mice were sensitized with recombinant Der p 2 (rDer p 2) and Der p followed by LNIT with rDer p 2 in conjunction with FIP. After intratracheal challenge with rDer p 2 and Der p, the airway inflammation was determined by analyzing the cell subpopulation and cytokine concentration in the bronchoalveolar lavage fluid. The allergen-specific IgE, IgG2a and IgG in the sera and IgA in the saliva were measured by ELISA. RESULTS: LNIT with rDer p 2 in conjunction with FIP could downregulate the lymphocyte infiltration in both rDer p 2- and Der p-induced airway inflammation. Both total and specific IgA in the saliva were increased after LNIT. Serum levels of IL-4, IL-10 and specific IgE were reduced and the specific IgG2a and IgG increased after LNIT. After LNIT, there was a reduction of airway hypersensitivity at 30 min after allergen challenge in the rDer p 2-and Der p-sensitized mice, with a significant decrease only in rDer p 2-sensitized mice. CONCLUSION: LNIT with rDer p 2 in conjunction with FIP was not only able to suppress rDer p 2-induced airway inflammation but also generate suppression of Der p-induced airway inflammation. The simultaneous reduction of IL-4 and IL-10 indicated that IL-10-producing cells were not activated by LNIT. The increment of IgA in the airway might play a role in the prevention of airway inflammation.

Administration, Intranasal↗
PubMed2005

Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation.

BACKGROUND: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. METHODS: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. RESULTS: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%; p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%; p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. CONCLUSION: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis.

Adult↗
PubMed1995

Plain X-ray films and air enema films reflect severe mucosal inflammation in acute ulcerative colitis.

In a prospective study of 34 patients with active ulcerative colitis, the findings of inflammation on plain abdominal films and air enema films were compared to those at colonoscopy including biopsy within 10 days. The degree of inflammation on X-ray films was graded independently by two radiologists, at colonoscopy by one gastroenterologist and from histological slides from 6 different colon segments by one pathologist for each patient. Air enema films had a high sensitivity for endoscopically confirmed friable or ulcerated mucosa (0.91). There was a high specificity (0.86) when excluding inflammation in individual colon segments. Absence of fecal residue as an indication of active inflammation had the same positive predictive value, 0.95, as an abnormal air enema film, 0.98 for endoscopically confirmed inflamed mucosa. The presence of fecal residue or a normal air enema film excluded a friable or ulcerated mucosa at endoscopy with negative predictive values of 0.83 and 0.86, respectively. Patients who had had a complete colonoscopy (n = 16) were divided into groups with total, extensive or distal colitis. Air enema films underestimated the extent of inflammation in 8 of 16 patients compared to colonoscopy. Of 6 patients with distal disease only on air enema films, 5 had disease above the splenic flexure at endoscopy. In patients with ulcerative colitis (1) the presence of fecal residue and a normal air enema film exclude a friable or ulcerated mucosa with a high degree of certainty, and (2) the absence of fecal residue and an abnormal air enema film are predictors of the presence of endoscopically confirmed inflammation.

Adult↗
PubMed2005

Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation.

RATIONALE: Emphysema is one component of chronic obstructive pulmonary disease (COPD), a respiratory disease currently increasing in prevalence worldwide. The mainstay therapy adopted to treat patients with COPD is glucocorticoids; unfortunately, this treatment has limited impact on disease symptoms or underlying airway inflammation. OBJECTIVE: There is an urgent need to develop therapies that modify both the underlying inflammation, thought to be involved in disease progression, and the structural changes in the emphysematous lung. METHODS: We have characterized an elastase-driven model of experimental emphysema in the rat that demonstrates COPD-like airway inflammation and determined the impact of a clinically relevant glucocorticoid. MEASUREMENTS AND MAIN RESULTS: We observed an increase in lung neutrophils, lymphomononuclear cells, mucus production, and inflammatory cytokines. Also present were increases in average air space area, which are associated with emphysema-like changes in lung function, such as increased residual volume and decreased flow; these increases in area were maintained for up to 10 weeks. In addition, we observed that elastase-induced airway neutrophilia is steroid resistant. Interestingly, the inflammation observed after elastase administration was found to be temporally associated with a lack of nuclear factor-kappaB pathway activation. This apparent nuclear factor-kappaB-independent inflammation may explain why treatment with a glucocorticoid was ineffective in this preclinical model and could suggest parallels in the steroid-resistant human disease. CONCLUSION: We believe that this model, in addition to its suitability for testing therapies that may modify existing emphysema, could be useful in the search for new therapies to reduce the steroid-resistant airway inflammation evident in COPD.

Algorithms↗
PubMed1999

CD23 and allergic pulmonary inflammation: potential role as an inhibitor.

CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8(+) T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity.

Animals↗
PubMed1990

Interleukin 1 suppresses inflammation in rabbit colitis. Mediation by endogenous prostaglandins.

Pretreatment with low-dose IL-1 has protective effects in animal models of inflammation or tissue injury, but the mechanisms of these protective effects are not established. To determine if prostaglandins are involved, we administered human recombinant IL-1 beta and measured rectal PGE2 production in rabbits with formalin-immune complex colitis. IL-1 beta (0.3 micrograms/kg) administered 24 h before induction of colitis increased PGE2 (231 +/- 36 to 1,299 +/- 572 pg/ml, P less than 0.01) and reduced subsequent inflammatory cell infiltration index (from 2.8 +/- 0.3 to 1.4 +/- 0.3, P less than 0.02) and edema (from 2.5 +/- 0.3 to 1.3 +/- 0.3, P less than 0.01) compared with vehicle-matched animals. Administration of ibuprofen (10 mg/kg i.v.) together with IL-1 beta prevented the stimulation of PGE2 and the reduction in inflammation. Colonic PGE2 production correlated inversely with subsequent severity of inflammation (P less than 0.02, r = -0.39) and edema (P less than 0.04, r = -0.35). IL-1-administration 30 min before induction of colitis did not affect the severity of inflammation. Similarly, pretreatment with a noninflammatory synthetic peptide (fragment 163-171) of human IL-1 beta, either 30 min or 24 h before colitis induction, did not reduce inflammation or increase prostaglandin synthesis. These data demonstrate that pretreatment with IL-1 beta 24 h before the induction of colitis reduces inflammation by a mechanism that requires prostaglandin synthesis.

Animals↗