Interleukin‐4 inhibits lipopolysaccharide‐induced expression of prostaglandin H synthase‐2 in human alveolar macrophages

Several studies have shown that interleukin‐4 (IL‐4) down‐regulates synthesis of prostaglandin E 2 (PGE 2 ). We evaluated the mechanisms for this suppression in human alveolar macrophages (HAMs). Normal HAMs were obtained from healthy nonsmoking volunteers. The cells either remained unstimulated, or were exposed to 10 μg/ml of lipopolysaccharide (LPS) and/or various amounts of IL‐4. LPS alone induced the synthesis of large amounts of PGE 2 and prostaglandin H synthase‐2 (PGHS‐2) protein. This effect of LPS was suppressed by increasing amounts of IL‐4. Expression of LPS‐induced PGHS‐2 mRNA was also inhibited by IL‐4. In addition, IL‐4 inhibited expression of CD14, which is a receptor for LPS bound to the LPS‐binding protein (LBP). We conclude that IL‐4 down‐regulates LPS‐induced release of PGE 2 , by reducing expression of the enzyme, PGHS‐2. One potential mechanism for this effect of IL‐4 is a reduced expression of CD14, which is the LPS‐LBP receptor. © 1995 Wiley‐Liss Inc.