Inhibition of lipopolysaccharide‐induced in vitro desensitization by interferon‐γ

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Abstract
Exposure of Mono‐Mac‐6 cells to lipopolysaccharide (LPS) can induce rapid and transient expression of cytokines like tumor necrosis factor (TNF), interleukin 1 and interleukin 6. Preculture of Mono‐Mac‐6 cells in culture medium containing small amounts (1—50 ng/ml) of LPS for 3 days leads to an unresponsiveness to a subsequent stimulation with a high amount of LPS. This in vivo, desensitization of a monocytic cell line may serve as a model for desensitization to LPS seen in vivo, for example in mice or man repetitively treated with LPS. Addition of interferon‐γ (IFN‐γ) to the Mono‐Mac‐6 cells during the LPS preculture period leads to an inhibition of desensitization, whereas addition of IFN‐α or IFN‐β is not able to inhibit the LPS‐induced desensitization. The inhibition of desensitization by IFN‐γ was dose dependent and time dependent. Preculture of Mono‐Mac‐6 cells with LPS leads to a strong reduction of TNF mRNA. This reduction of specific mRNA is also overcome by addition of IFN‐γ, but not by IFN‐α and IFN‐β, indicating that pretranslational mechanisms are responsible for the regulation of TNF in desensitization.

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