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.