Cytokine Production from Peripheral Whole Blood in Atopic and Nonatopic Asthmatics: Relationship with Blood and Sputum Eosinophilia and Serum Ige Levels
[en] BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is known about nonatopic asthma. METHODS: We have compared the production of IL-4, IL-6, IFN-gamma, and TNF-alpha from peripheral blood leukocytes between atopic (n=21) and nonatopic (n=22) asthmatics and healthy nonatopic subjects (n=20). Peripheral blood was incubated for 24 h either without stimulus or with LPS or PHA. Cytokines were measured by the immunotrapping technique (Dynamic Immunoassay). RESULTS: When compared to healthy nonatopic subjects, both atopic and nonatopic asthmatics showed increased blood and sputum eosinophilia associated with raised total serum IgE levels. Similarly, both asthma groups displayed spontaneous, endotoxin-induced overproduction of IL-6. Enhanced spontaneous, endotoxin-induced release of IL-4 combined with reduced spontaneous IFN-gamma production was seen only in atopic asthma. In this group of patients, the production of IL-4 was related to the extent of blood and sputum eosinophilia. In nonatopic asthmatics, serum levels of IgE were inversely related to the production of IFN-gamma. CONCLUSIONS: Both atopic and intrinsic asthma display raised blood and airway eosinophilia, raised total serum IgE, and overproduction of IL-6 from peripheral blood. Atopic asthma is also characterized by impaired spontaneous release of IFN-gamma and increased production of IL-4 that correlates with the magnitude of eosinophilic inflammation.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Bettiol, J.
Bartsch, Pierre ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
De Groote, D.
Gevaerts, Y.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Language :
English
Title :
Cytokine Production from Peripheral Whole Blood in Atopic and Nonatopic Asthmatics: Relationship with Blood and Sputum Eosinophilia and Serum Ige Levels
Bousquet J., Chanez P., Lacoste J. (1990) Eosinophilic inflammation in asthma. N Engl J Med 323:1033-1039.
Kay A.B. (1996) Th2-type cytokines in asthma. Ann N Y Acad Sci 796:1-8.
Rackeman F.M. (1947) A working classification of asthma. Am J Med 3:601-606.
Godard D., Bousquet J., Michel F.B. (1997) Extrinsic and intrinsic asthma: Still a matter of debate?. Clln Asthma Rev 1:19-22.
Wuthrich B., Schindler C., Leuenber P., Ackerman-Liebrich U. (1995) Prevalence of atopy and pollinosis in the adult population of Swizerland (SAPALDIA Study). Swiss Study on Air Pollution and Lung Diseases in Adults. Int Arch Allergy Immunol 106:149-146.
Menz G., Ying S., Durham S.R. (1998) Molecular concepts of IgE-initiated inflammation in atopic and nonatopic asthma. Allergy 53:15-21.
Walker C., Bode E., Boer L., Hansel T.T., Blaser K., Virchow J.C. (1992) Allergic and nonallergic asthmatics have distinct pattern of T cell activation and cytokine production in peripheral blood and BAL. Am Rev Respir Dis 146:109-115.
Tang C., Rolland J.M., Ward C., Quan B., Walters E.H. (1997) IL-5 production by bronchoalveolar lavage and peripheral blood mononuclear cells in asthma and atopy. Eur Respir J 10:624-632.
Humbert M., Durham S., Ying S. (1996) IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: Evidence against 'intrinsic' asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med 154:1497-1504.
Humbert M., Grant A., Taborda-Barata L. (1996) High-affinity IgE receptor (FcεRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma. Am J Respir Crit Care Med 153:1931-1937.
De Groote D., Gevaerts Y., Lopez M. (1993) Novel method for the measurement of cytokine production by a one-stage procedure. J Immunol Methods 163:259-267.
Mosman T.R., Coffman R.L. (1989) Th1 and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol 7:145-173.
Kishimoto T. (1989) The biology of IL-6. Blood 74:1-10.
Kips J.C., Tavernier J.H., Joos G.F., Peleman R.A., Pauwels R.A. (1993) The potential role of tumor necrosis factor α in asthma. Clin Exp Allergy 23:247-250.
Louis R., Bury T., Corhay J.L., Radermecker M. (1993) No increase in plasma histamine during PAF induced bronchoconstriction in allergic asthmatics. Chest 104:806-810.
Louis R., Shute J., Biagi S. (1997) Cell infiltration, ICAM-1 expression and eosinophil chemotactic activity in asthmatic sputum. Am J Respir Crit Care Med 155:466-472.
Burrows B., Martinez F.D., Halonen M., Barsee R.A., Cline M.G. (1989) Association of asthma with serum IgE levels and skintest reactivity to allergens. N Engl J Med 320:271-277.
Sanchez-Guerrero I.M., Herrero N., Muro M. (1997) Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4 dependent IgE. Eur Respir J 10:2091-2096.
McHugh S.M., Wilson A.B., Deighton J., Lachman P.J., Ewan P.W. (1994) The profiles of interleukin (IL)-2, IL-6 and interferongamma production by peripheral blood mononuclear cells from house dust mite allergic patients: A role for IL-6 in allergic disease. Allergy 49:751-759.
Yokoyama A., Kohno N., Fujino S. (1995) Circulating interleukin-6 levels in patient with bronchial asthma. Am J Respir Crit Care Med 151:1354-1358.
Louis E., Belaiche J., Van Kemseke C. (1997) A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn's disease. Eur J Gastroenterol Hepatol 9:939-944.
Vercelli D., Jabara H.H., Arai K.-I., Yokota T., Geha R.S. (1989) Endogenous interleukin-6 plays an obligatory role in interleukin-4 dependent human IgE synthesis. Eur J Immunol 19:1419-1424.
Gagnon R., Akoum A., Hebert J. (1993) Lol p I-induced IL-4 and IFN-γ production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season. J Allergy Clin Immunol 91:950-956.
Tang C., Rolland J., Ward C., Bisch R., Thien F., Walters E.H. (1996) Seasonal comparison of cytokine profiles in atopic asthmatics and atopic nonasthmatics. Am J Respir Crit Care Med 154:1615-1622.
Brunner T., Heusser C.H., Dahinden C.A. (1993) Human peripheral blood basophils primed by interleukin 3 produce IL-4 in response to immunoglobulin E receptor stimulation. J Exp Med 177:605-611.
Nonaka M., Nonaka R., Wooley K. (1995) Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and released by peripheral blood eosinophils. J Immunol 155:3234-3244.
Thornhill M.H., Wellicome S.M., Mahiouz D.L., Lanchbury J.S., Kyan-Aung U., Haskard D.O. (1991) Tumor necrosis factor combines with IL-4 or IFN-γ to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent mechanisms. J Immunol 146:592-598.
Bruselle G., Kips J., Joos G., Bluethmann H., Pauwels R. (1995) Allergen-induced airway inflammation and bronchial responsiveness in wild type and interleukin-4-deficient mice. Am J Respir Cell Mol Biol 12:254-259.
Molet S., Ramos-Barbon D., Martin J.G., Hamid Q. (1999) Adoptively transferred late allergic response is inhibited by IL-4, but not IL-5, antisense oligonucleotide. J Allergy Clin Immunol 104:205-214.
Krug N., Madden J., Redington A. (1996) T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 14:319-326.
Cembrzynska-Nowack M., Szklark E., Inglot A.D., Teodorczyk-Injeyan J.A. (1993) Elevated release of tumor necrosis factor-alpha and interferon-gamma by bronchoalveolar leukocytes from patients with bronchial asthma. Am Rev Respir Dis 147:291-295.
