ANTIINFLAMMATORY EFFECTS OF NEDOCROMIL SODIUM - INHIBITION OF ALVEOLAR MACROPHAGE FUNCTION

The IgE-dependent activation of mononuclear phagocytic cells through their capacity to express low affinity IgE receptors (FcepsilonRII) has been proposed as a mechanism for the development of airways inflammation in allergic asthma. This FcepsilonRII expression leads to the IgE-dependent production of the potent pro-inflammatory cytokines IL-1beta and TNF-alpha. Expression by monocytes of FcepsilonRII is regulated by several cytokines including interleukin-4, gamma- and alpha-interferons, and granulocyte-macrophage and macrophage colony stimulating factors. An anti-inflammatory effect of nedocromil on monocytes has been proposed as a possible mechanism for its anti-asthma activity. We therefore investigated the capacity of nedocromil to modulate mononuclear phagocyte FcepsilonRII expression and cytokine production. We used an anti-FcepsilonRII antibody and flow cytometric analysis to assess the capacity of nedocromil to modulate cytokine-induced FcepsilonRII expression in normals and asthmatics. Monocytes, THP-1 monocyte leukaemia cells, and alveolar macrophages were exposed to varying concentrations of these cytokines for 48 hr at 37-degrees-C with or without the additional presence of nedocromil (1-10 mum) and the per cent of monocytes expressing FcepsilonRII was determined. No changes in FcepsilonRII expression were observed. Subsequently, we investigated the capacity of nedocromil to affect the capacity of IgE plus anti-IgE complexes, allergen, and LPS (16 hr/37-degrees-C) to stimulate IL-1beta and IL-6 production. No changes were observed when nedocromil was applied concomitant with the stimulus. However, pre-treatment (30 min) with nedocromil was associated with a 59.5 +/- 5.6% inhibition of IL-6 production stimulated by allergen and 34.5 +/- 5.1% by anti-IgE. In conclusion, nedocromil does not modulate mononuclear phagocytic cell FcepsilonRII expression but does suppress IgE-dependent cytokine production. This may represent an important anti-inflammatory action of nedocromil in the treatment of reactive obstructive airways disease.