Down-regulation by interleukin 4 of activation of human alveolar macrophages to the tumoricidal state.
The effect of recombinant human interleukin 4 (IL-4) on the expression of antitumor activity of human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined. AM were incubated for 16 h in medium with various macrophage activators [lipopolysaccharide, des-methyl muramyldipeptide, Nocardia rubra cell wall skeleton, and heptanoyl-gamma-D-Glu-(L)-meso-alpha,epsilon-A2pm(L)-D-Al aOH] in the presence or absence of IL-4, and then their tumoricidal activity was assayed by measuring 125I-UdR release from human melanoma (A375) cells. The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4 in 3 of 7 donors. Addition of IL-4 to cultures of AM with the activators resulted in dose-dependent suppression of AM-mediated cytotoxicity against A375 cells. IL-4 also inhibited AM-mediated cytotoxicity against A375-R cells, which are resistant to interleukin 1 (IL-1) and tumor necrosis factor alpha, HT-29 colon cancer cells, and KB cells. IL-4 inhibited the early induction phase of AM activation. Pretreatment of AM with IL-4 also suppressed their expression of antitumor activity in response to lipopolysaccharide. IL-4 inhibited the production of monokines (IL-1 and tumor necrosis factor alpha) by AM at the protein and mRNA levels. These findings suggest that IL-4 may be important in vivo in the down-regulation of antitumor expression of AM in the lung by inhibiting the production of monokines and other killing mechanisms.
Nishioka
Y
Y
Third Department of Internal Medicine, The University of Tokushima School of Medicine, Japan.
Sone
S
S
Orino
E
E
Nii
A
A
Ogura
T
T
D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4