Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs

Clinical and Experimental Immunology - Tập 89 Số 3 - Trang 347-350 - 2008
A.A. Norris1, D M Jackson1, R P Eady1
1Department of Pharmacology, Fisons plc, Loughborough, UK

Tóm tắt

SUMMARY A close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.

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Tài liệu tham khảo

Denburg, 1989, Basophil mast cell and eosinophil growth and differentiation factors in human allergic disease, Clin Exp Allergy, 19, 249, 10.1111/j.1365-2222.1989.tb02379.x

Owen, 1987, Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts, J Exp Med, 168, 129, 10.1084/jem.166.1.129

Lopez, 1988, Recombinant human IL5 is a selective activator of human eosinophil function, J Exp Med, 167, 219, 10.1084/jem.167.1.219

Rothenberg, 1988, Human eosinophils have prolonged survival, enhanced functional properties and become hypodense when exposed to human interleukin-3, J Clin Invest, 81, 1986, 10.1172/JCI113547

Yamaguchi, 1988, Highly purified murine interleukin-5 (IL-5) stimulates eosinophil function and prolongs in vitro survival, J Exp Med, 167, 1737, 10.1084/jem.167.5.1737

Corrigan, 1988, T lymphocyte activation in acute severe asthma, Lancet, i, 1129, 10.1016/S0140-6736(88)91951-4

Azzawi, 1990, Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma, Am Rev Resp Dis, 142, 1407, 10.1164/ajrccm/142.6_Pt_1.1407

Corrigan, 1990, T lymphocyte activation in acute severe asthma, Am Rev Resp Dis, 141, 970, 10.1164/ajrccm/141.4_Pt_1.

Gleich, 1984, Asthma III. Pathophysiology, immunopharmacology and treatment, 195

Durham, 1985, Eosinophils, bronchial hyperreactivity and late asthmatic reactions, Clin Allergy, 15, 411, 10.1111/j.1365-2222.1985.tb02290.x

Bousquet, 1990, Eosinophilic inflammation in asthma, N Engl J Med, 323, 1033, 10.1056/NEJM199010113231505

Frew, 1988, The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man, J Immunol, 141, 4158

Gonzalez, 1987, Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cell in asthma, Am Rev Resp Dis, 136, 600, 10.1164/ajrccm/136.3.600

Frew, 1990, T lymphocytes and eosinophils in allergen-induced late-phase asthmatic reactions in the guinea-pigs, Am Rev Resp Dis, 141, 407, 10.1164/ajrccm/141.2.407

Martinet, 1988, Evaluation of the in vitro and in vivo effects of cyclosporine on the lung T-lymphocyte alveolitis of active pulmonary sarcoidosis, Am Rev Resp Dis, 138, 1242, 10.1164/ajrccm/138.5.1242

Mullarkey, 1986, Methotrexate in the treatment of steroid-dependent asthma, Ann Allergy, 56, 347

Mullarkey, 1988, Methotrexate in the treatment of corticosteroid-dependent asthma, N Engl J Med, 318, 603, 10.1056/NEJM198803103181004

Pacheco, 1985, Azathioprine treatment of chronic pulmonary sarcoidosis, Sarcoidosis, 8, 107

Borel, 1976, Biological effects of cyclosporin A: a new anti-lymphocytic agent, Agents Actions, 6, 468, 10.1007/BF01973261

Kino, 1987, FK506, a novel immunosuppressant isolated from A. streptomyces. II Immunosuppressant effect of FK506 in vitro, J Antibiotics, XL, 1256, 10.7164/antibiotics.40.1256

Hutson, 1988, Early and late-phase bronchoconstriction after allergen challenge of non-anesthetised guinea-pigs, Am Rev Resp Dis, 137, 548, 10.1164/ajrccm/137.3.548

Kimura, 1973, Basophils in bronchial asthma with reference to reagin-type allergy, Clin Allergy, 3, 195, 10.1111/j.1365-2222.1973.tb01321.x

Gulbenkian, 1990, Anaphylactic challenge causes eosinophil accumulation in bronchoalveolar lavage fluid of guinea-pigs, Am Rev Resp Dis, 142, 680, 10.1164/ajrccm/142.3.680

Kings, 1990, Human recombinant lymphokines and cytokines induce pulmonary eosinophilia in the guinea-pig which is inhibited by ketotifen and AH 21-132, Int Arch Allergy Appl Immunol, 91, 354, 10.1159/000235141

Etienne, 1989, Modulation by drugs of eosinophil recruitment induced by immune challenge in the rat, Int Arch All Appl Immunol, 88, 216, 10.1159/000234790

Touvay, 1989, Effect of cyclosporin A and the platelet-activating factor (PAF) antagonist, BN 52021, on PAF- and antigen-induced bronchoconstriction in the guinea-pig, Biochem Biophys Res Comm, 163, 118, 10.1016/0006-291X(89)92107-4

Arima, 1990, Cyclosporin A inhibits allergen-induced late asthmatic response and increase of airway hyperresponsiveness in guinea-pigs, Am Rev Resp Dis, 141, A475

Yoshimura, 1989, Effect of a new immunosuppressant agent, FK506, on human lymphocyte responses in vitro: I. FK506 inhibits the expression of alloantigen-activated suppressor cells as well as the induction of alloreactivity, Transplantation, 47, 351, 10.1097/00007890-198902000-00034

Ohtoshi, 1991, Monocyte-macrophage differentiation induced by human upper airway epithelial cells, Am J Resp Cell Mol Biol, 4, 255, 10.1165/ajrcmb/4.3.255

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Clinical and Experimental Immunology

Tập 89 Số 3

347-350

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