Differential effects of interleukin-4 on superoxide anion production by human alveolar macrophages stimulated with lipopolysaccharide and interferon-gamma.
The effect of interleukin-4 (IL-4) on the activation state of human alveolar macrophages (AMs) and blood monocytes induced by lipopolysaccharide (LPS) or recombinant interferon-gamma (IFN-gamma) was investigated on the basis of their ability to produce superoxide anion (O2-). AMs were obtained from healthy donors by bronchoalveolar lavage, and O2- productions of these cells were assayed by a cytochrome c reduction method after incubation with stimulants for 24 h. AMs produced more O2- than autologous blood monocytes when stimulated with LPS. IL-4 alone had little effect on O2- production by unstimulated AMs but down-regulated O2- production by LPS-stimulated AMs in a dose-dependent manner. IL-4 also suppressed O2- production by AMs induced by the synergistic actions of muramyl dipeptide (norMDP) and IFN-gamma. Maximum suppression by IL-4 of O2- production by AMs was observed when IL-4 was added within 1 h after initiation of LPS stimulation. AMs also showed high O2- production when stimulated with IFN-gamma alone. In contrast to its suppression of O2- production by LPS-stimulated AMs, IL-4 enhanced O2- production by AMs stimulated with IFN-gamma. These data suggest that IL-4 is an important regulator of O2- production by macrophages through different pathways depending on the stimulus.
Bhaskaran
G
G
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Nii
A
A
Sone
S
S
Ogura
T
T
D000328:Adult; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D008070:Lipopolysaccharides; D013481:Superoxides; D015847:Interleukin-4; D007371:Interferon-gamma