Alveolar macrophages of allergic resistant and susceptible strains of ratsshow distinct cytokine profiles

Brown Norway rats are widely used as a model of asthma, whereas Sprague Daw ley rats do not develop allergic reactions under the same conditions. Given the importance of alveolar macrophages (AM) in down-regulating cellular im mune responses in the lung, we postulated that the different susceptibiliti es in the development of airway allergic reactions in these rat strains may be related to functional differences in their AM. We investigated the prod uction of important mediators in asthma, namely tumour necrosis factor (TNF ), interleukin-10 (IL-10), IL-12, IL-13, nitric oxide (NO) and macrophage i nflammatory protein-1 alpha (MIP-1 alpha), by AM of unsensitized Sprague Da wley and Brown Norway rats. AM were purified by adherence and stimulated wi th OX8 (anti-CD8 antibody) or LPS. OX8 stimulation significantly increased the release of TNF, IL-10 and NO in both strains of rats, whereas MIP-1 alp ha and IL-12 release were increased in Brown Norway rats only. Interestingl y, stimulated AM from Sprague Dawley rats released significantly more TNF a nd less IL-10, IL-12, IL-13, MIP-1 alpha and NO compared with AM from Brown Norway rats. These differences were also observed at the mRNA level, excep t for TNF. Thus, AM from Brown Norway and Sprague Dawley rats are functiona lly different. Furthermore, LPS- and OX8-stimulated AM from Brown Norway ra ts produce more Th2 type cytokines (IL-10 and IL-13) than AM from Sprague D awley rats, suggesting that these cells may play an important role in creat ing a cytokine milieu that may favour the development of allergic reactions .