INTERLEUKIN-4 SUPPRESSES INFLAMMATORY CYTOKINE GENE-TRANSCRIPTION IN PORCINE MACROPHAGES

Inflammatory cytokines, including interleukin (IL)-1 alpha, IL-1 beta, IL-8, and tumor necrosis factor alpha (TNF-or) are produced by macrop hages in response to a variety of pathogenic stimuli. We show here tha t the expression of inflammatory cytokines is suppressed by IL-4 at th e transcriptional level. Interleukin-4, when added together with bacte rial lipopolysaccharide (LPS), suppressed LPS-induced increases in mRN A levels of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in alveolar mac rophages. The level of suppression was dependent on dose and time of e xposure and reached a maximum of 75-80% of uninduced values for IL-1 a lpha, IL-8, and TNF. Interleukin-1 beta expression was completely inhi bited by IL-4. The amount of secreted protein, as determined by TNF-al pha bioassay, was also suppressed by IL-4. Half-maximal suppression oc curred at IL-4 concentrations between 0.02 and 0.1 ng/ml for all infla mmatory cytokines, Nuclear run-on assays showed that IL-4 suppressed t ranscriptional activity of all inflammatory cytokines. Messenger RNA s tability was not changed by IL-4. The data suggest that IL-4 plays an important transcriptional role in the regulation of alveolar macrophag e inflammatory activities in respiratory disease and raise the possibi lity that IL-4 may function in vivo as a coordinator of inflammatory a nd immune responses.