Potentiates the Release of TNF- a and MIP-1 a by Alveolar Macrophages during Allergic Reactions

Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFNg can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factora (TNFa ) and macrophage inflammatory protein-1 a (MIP-1 a ). Given the importance of these cytokines, we have investigated the effect of IFNg on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis –infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fc « RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNFa release (153 6 48 pg/10 6 cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNFa in rat alveolar macrophages was also increased by stimulation with IgE/anti-IgE. Treatment with IFNg prior to stimulation with IgE/anti-IgE showed a timeand concentration-dependent increase of TNFa release. Interestingly, IgE/anti-IgE treatment did not stimulate the release of MIP-1 a (15 6 5 pg/10 6 cells), but IFNg treatment alone and with IgE/anti-IgE significantly increased and potentiated MIP-1 a release (98 6 40 pg/10 6 cells) by alveolar macrophages, respectively. These results suggest that IFNg produced at times such as during viral infections primes alveolar macrophages for enhanced release of inflammatory mediators during allergic reactions, thereby contributing to the inflammatory process. Déry, R. E., and E. Y. Bissonnette. 1999. IFNg potentiates the release of TNFa and MIP-1 a by alveolar macrophages during allergic reactions. Am. J. Respir. Cell Mol. Biol. 20:407–412.