Human Recombinant Lymphokines and Cytokines Induce Pulmonary Eosinophilia in the Guinea Pig which Is Inhibited by Ketotifen and AH 21–132

Kings, M A; Chapman, Ian; Kristersson, A; Sanjar, Shahin; Morley, John E.

doi:10.1159/000235141

Cited by 39 publications

(14 citation statements)

References 41 publications

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“…While in the present study both heparin and Org 10172 inhibited the infiltration of inflammatory cells into the airways following PAF challenge, it appears that the inhibitory effect of heparin on PAF-induced airway hyperresponsiveness is not dependent on this anti-inflammatory effect as polyglutamic acid substantially inhibited cell infiltration without inhibiting the associated airway hyperresponsiveness. These results, separating the induction of bronchial hyperresponsiveness from inflammatory cell infiltration, support previous work in this model with other drug classes (Spina et al, 1991;Herd et al, 1992) and in other experimental (Ladenius & Biggs, 1989;Kings et al, 1990;Sanjar et al, 1990;Matsuse et al, 1991) and clinical (Lundgren et al, 1988;Gibson et al, 1989) situations, showing that eosinophils may not be a prerequisite for the induction of airway hyperresponsiveness.…”

Section: Bronchoalveolar Lavagesupporting

confidence: 90%

Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits

Sasaki

Herd

Page

1993

British J Pharmacology

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We have investigated the effect of an unfractionated heparin preparation, a low‐molecular weight heparinoid (Org 10172) and the polyanionic molecule polyglutamic acid against PAF‐induced airway hyperresponsiveness and pulmonary cell infiltration in neonatally immunized rabbits in vivo. Exposure of neonatally immunized rabbits to aerosolized platelet activating factor (PAF) (80 μg ml−1 for 60 min) elicited an increase in airway responsiveness to inhaled histamine 24 h and 72 h following challenge which was associated with an infiltration of inflammatory cells into the airways, as assessed by bronchoalveolar lavage (BAL). A significant increase in the total numbers of cells recovered from BAL fluid was associated with significantly increased cell numbers of neutrophils, eosinophils and mononuclear cells 24 h following PAF exposure. The numbers of eosinophils and neutrophils in the airways remained elevated 72 h after challenge. The intravenous administation of an unfractionated preparation of heparin (100 units kg−1) or Org 10172 (100 μg kg−1) 30 min prior to PAF exposure significantly inhibited the airway hyperresponsiveness induced by PAF, 24 h and 72 h following challenge. PAF‐induced hyperresponsiveness was not significantly affected by prior intravenous administration of polyglutamic acid (100 μg kg−1). The intravenous administration of unfractionated heparin (100 units kg−1), Org 10172 (100 μg kg−1) or polyglutamic acid (100 μg kg−1) 30 min prior to PAF exposure significantly inhibited the expected increase in total cell infiltration. This study shows that unfractionated heparin and a low‐molecular weight heparinoid, Org 10172, are capable of inhibiting both the airway hyperresponsiveness and pulmonary cell infiltration induced by PAF in the rabbit.

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Section: Bronchoalveolar Lavagesupporting

confidence: 90%

Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits

Sasaki

Herd

Page

1993

British J Pharmacology

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“…T-cell derived cytokines such as GM-CSF, IL-3 and IL-5 have pronounced effects on neutrophils and eosinophils, including chemotaxis, prolongation of survival and activation (Corrigan & Kay, 1992). Human recombinant GM-CSF and IL-3 have been shown to induce eosinophilia in the guineapig (Kings et al, 1990) and intra-tracheal injection of murine recombinant (mr) IL-5 induced a significant cellular infiltration into guinea-pig lungs (Iwama et al, 1992). It is interesting to note that there was a significant increase in lymphocytes counts in BAL fluid from Sephadex-injected guinea-pigs although the role of these cells in the model is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Inhibition by rapamycin of leukocyte migration and bronchial hyperreactivity induced by injection of Sephadex beads to guinea‐pigs

Francischi

Conroy

Maghni

et al. 1993

British J Pharmacology

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1 The effect of rapamycin (0.001 to 5 mg kg-') on the increased leukocyte counts in bronchoalveolar lavage (BAL) fluid and hyperreactivity of isolated bronchial strips to histamine and acetylcholine (ACh) was studied following the intravenous injection of Sephadex beads to guinea-pigs.2 The intramuscular (i.m.) injection of rapamycin (0.012 to 5 mg kg-') dose-dependently inhibited the increase in leukocyte counts in BAL fluid. Rapamycin (5 mg kg-1) reduced the numbers of eosinophils neutrophils, macrophages and lymphocytes in BAL fluid by 64, 55, 19 and 50% respectively. In addition, rapamycin (0.0 12 to 5 mg kg-') significantly inhibited the Sephadex-induced hyperreactivity of bronchial tissue to both histamine and ACh.3 At a dose of 0.001 mg kg-', rapamycin did not significantly reduce leukocyte infiltration or bronchial hyperreactivity. 4 Cyclosporin (5 mg kg-') significantly reduced both lymphocyte and eosinophil numbers in BAL fluid of Sephadex-injected guinea-pigs whereas dexamethasone (1 mg kg-') significantly reduced lymphocyte numbers. Neither drug affected the bronchial hyperreactivity to histamine and ACh. 5 It is concluded that the new immunosuppressive drug, rapamycin, is a potent inhibitor of leukocyte migration and bronchial hyperreactivity observed following the intravenous injection of Sephadex beads to guinea-pigs. Rapamycin also appears to be more effective than cyclosporin or dexamethasone in reducing leukocyte counts and bronchial hyperreactivity in this model. 6 Our results suggest that inflammatory mechanisms which are inhibited by rapamycin may be important in the induction of Sephadex-induced hyperreactivity.

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“…Pretreat ment with aminophylline, ketotifen or dexamethasone prevented eosinophilia but not hyperreactivity. Following subcutaneous or intraperitoneal administration of recom binant human granulocyte-macrophage colony-stimulat ing factor or interleukin-3 in guinea pigs, Kings et al [24] reported eosinophilia in the BALF but found no signs of increased bronchial reactivity to i.v. histamine.…”

Section: Discussionmentioning

confidence: 99%

Intratracheal Application of Sephadex in Rats Leads to Massive Pulmonary Eosinophilia without Bronchial Hyperreactivity to Acetylcholine

Kubin¹,

Deschl²,

Linssen³

et al. 1992

Int Arch Allergy Immunol

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Fourteen Brown-Norway rats were pretreated with physiological saline (n = 7) or 500 μg Sephadex (n = 7) intratracheally. 24 h later, a bronchial provocation test was performed under pentobarbital anaesthesia using increasing doses of acetylcholine aerosol and the degree of bronchospasm was measured using a modified Konzett-Rössler method. Subsequently, leucocyte counts were determined in the bronchoalveolar lavage fluid (BALF), BALF cells were differentiated, and the chemiluminescence of the BALF leucocytes were measured. Finally, the lungs were removed and histologically examined. The cell count in the BALF was significantly (p < 0.05) increased in the animals pretreated with Sephadex compared to those in the saline group (mean value ± SEM: 0.38 ± 0.07 vs. 0.15 ± 0.02 × 10⁶/ml). This difference was also reflected in the chemiluminescence measurements (2.51 ± 0.53 vs. 0.20 ± 0.03 × 10⁶ counts/0.5 ml). In the Sephadex-treated animals there was also a significant increase in the absolute number of neutrophil (0.040 ± 0.010 vs. 0.011 ± 0.002 × 10⁶/ml) and, in particular, eosinophil granulocytes (0.188 ± 0.055 vs. 0.003 ± 0.001 × 10⁶/ml) in the total leucocytes of the BALF. Lung histology showed massive perialveolar and peribronchial oedema and granulomatous infiltrates, primarily with eosinophils, after intratracheal application of Sephadex; these findings were not observed in the saline group. None of these changes in the rats pretreated with Sephadex manifested themselves in increased bronchial reactivity to acetylcholine aerosol. It is uncertain if the Sephadex-induced increase in the eosinophil count is accompanied by an activation of this cell population, which appears to be of importance for the occurrence of bronchial hyperreactivity. It is clear from this animal model that the presence of inflammatory cells in the BALF and lung tissue of rats does not in itself result in increased reactivity of the airways.

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Human Recombinant Lymphokines and Cytokines Induce Pulmonary Eosinophilia in the Guinea Pig which Is Inhibited by Ketotifen and AH 21–132

Cited by 39 publications

References 41 publications

Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits

Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits

Inhibition by rapamycin of leukocyte migration and bronchial hyperreactivity induced by injection of Sephadex beads to guinea‐pigs

Intratracheal Application of Sephadex in Rats Leads to Massive Pulmonary Eosinophilia without Bronchial Hyperreactivity to Acetylcholine

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