Interleukin‐4 suppresses inflammatory cytokine gene transcription in porcine macrophages

Inflammatory cytokines, including interleukin (IL)‐1α, IL‐1β, IL‐8, and tumor necrosis factor α(TNF‐α) are produced by macrophages in response to a variety of pathogenic stimuli. We show here that the expression of inflammatory cytokines is suppressed by IL‐4 at the transcriptional level. Interleukin‐4, when added together with bacterial lipopolysaccharide (LPS), suppressed LPS‐induced increases in mRNA levels of IL‐1α, IL‐1β, IL‐8, and TNF‐αin alveolar macrophages. The level of suppression was dependent on dose and time of exposure and reached a maximum of 75–80% of uninduced values for IL‐1α, IL‐8, and TNF. Interleukin‐1βexpression was completely inhibited by IL‐4. The amount of secreted protein, as determined by TNF‐αbioassay, was also suppressed by IL‐4. Half‐maximal suppression occurred at IL‐4 concentrations between 0.02 and 0.1 ng/ml for all inflammatory cytokines. Nuclear run‐on assays showed that IL‐4 suppressed transcriptional activity of all inflammatory cytokines. Messenger RNA stability was not changed by IL‐4. The data suggest that IL‐4 plays an important transcriptional role in the regulation of alveolar macrophage inflammatory activities in respiratory disease and raise the possibility that IL‐4 may function in vivo as a coordinator of inflammatory and immune responses J. Leukoc. Biol.56: 507–513; 1994.