Leukemia inhibitory factor induces interleukin-8 and monocyte chemotactic and activating factor in human monocytes: differential regulation by interferon-gamma

Leukemia inhibitory factor (LIF) is a cytokine released at the site of injuries where there is a recruitment of monocytes and polymorphonuclear cells. We analyzed the effect of LIF on human monocytes, which are a major source of chemotactic factors. We showed that supernatants of monocytes treated with LIF (50 ng/mL) for 18 hours had chemotactic activity for neutrophils and monocytes that was neutralized by anti-interleukin-8 (anti-IL-8) and anti-monocyte chemotactic and activating factor (anti-MCAF) neutralizing antibodies. Northern blot analysis showed induction of IL-8 and MCAF RNA in monocytes treated with LIF. Both IL-8 and MCAF mRNA were induced within 3 hours of stimulation. IL-8 and MCAF mRNAs expression peaked at 6 hours and 18 hours, respectively. Interferon-gamma (IFN-gamma), a potent monocyte activator, inhibited IL-8 induction by LIF. On the contrary, IFN-gamma by itself induced MCAF and did not affect the LIF- induced MCAF. These results indicate that LIF released at the site of injury by inducing IL-8 and MCAF can play an important role in recruiting leukocytes and that IFN-gamma can differentially regulate this recruitment.