Interleukin (IL)-9 is known to regulate many cell types involved in T-helper type 2 responses classically associated with
asthma, including B- and T-lymphocytes, mast cells, eosinophils and epithelial cells. In contrast, target cells mediating the effects of
IL-9 in the lower respiratory tract remain to be identified. Therefore, the authors evaluated the activity of
IL-9 on human alveolar macrophages (AM) from healthy volunteers. AM preincubated with
IL-9 before
lipopolysaccharide (LPS) stimulation exhibited a decreased oxidative burst, as previously shown with
IL-4. The inhibitory effect of
IL-9 was abolished by anti-hIL-9R alpha
monoclonal antibody, and presence of
IL-9 receptors on AM was demonstrated by immunofluorescence. Both
IL-4 and
IL-9 failed to modulate tumour
necrosis factor-alpha,
IL-8 and
IL-10 release by LPS-stimulated AM. However, several observations suggested that
IL-9 and
IL-4 act through different mechanisms: 1)
interferon-gamma antagonised the
IL4- but not the IL-9-mediated inhibition of AM oxidative burst; 2) expression of CD14 was downregulated by IL-4 but not by IL-9 and 3) production of tumour
growth factor-beta by activated AM was potentiated by IL-9 and not by
IL4, and was required for the IL-9-mediated inhibition of AM oxidative burst. These observations provide additional information concerning the activity of
interleukin-9 in the lung, related to inflammatory or fibrosing lung processes.