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Interferon-regulated Mx genes are not responsive to interleukin-1, tumor necrosis factor, and other cytokines
Abstract:
Accumulation of Mx gene products in cells of patients and experimental animals has been recognized as a useful marker for detecting minute quantities of biologically active interferon (IFN). Goetschy et al. (J. Goetschy, H. Zeller, J. Content, and M. A. Horisberger, J. Virol. 63:2616-2622, 1989) reported that not only IFNs but also interleukin-1 (IL-1) and tumor necrosis factor (TNF) were potent inducers of the human Mx genes. However, we observed no Mx induction in cultured human fibroblasts or in human peripheral blood mononuclear cells treated with various concentrations of IL-1 alpha or TNF-alpha. Mx induction was found in the spleens of mice treated with TNF-alpha or IL-1 alpha, but this effect could be neutralized with antibodies to murine IFN-alpha/beta. Of the other cytokines that we tested (IL-2, IL-6, and granulocyte-macrophage colony-stimulating factor), only IL-2 induced the Mx genes in peripheral blood mononuclear cells, but antibodies to human IFN-beta efficiently neutralized this effect. Our results thus indicate that IFNs are the only cytokines with intrinsic Mx-inducing activity.
Insights
Interferons (IFNs) are the sole cytokines with intrinsic Mx-inducing activity. Other cytokines like interleukin-1 (IL-1) and tumor necrosis factor (TNF) do not directly induce Mx genes, contrary to previous findings.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Mx gene products serve as biomarkers for interferon (IFN) activity.
- Previous research suggested interleukin-1 (IL-1) and tumor necrosis factor (TNF) could induce human Mx genes.
Purpose of the Study:
- To investigate the intrinsic Mx-inducing capabilities of various cytokines.
- To clarify the role of IL-1 and TNF in Mx gene induction.
Main Methods:
- Cultured human fibroblasts and peripheral blood mononuclear cells were treated with IL-1 alpha and TNF-alpha.
- Mice were treated with TNF-alpha or IL-1 alpha, and spleens were analyzed.
- Antibodies against IFN-alpha/beta and IFN-beta were used for neutralization experiments.
- Other cytokines including IL-2, IL-6, and granulocyte-macrophage colony-stimulating factor were tested.
Main Results:
- IL-1 alpha and TNF-alpha did not induce Mx genes in human cells.
- Mx induction in mouse spleens treated with IL-1 alpha or TNF-alpha was neutralized by anti-IFN-alpha/beta antibodies.
- IL-2 induced Mx genes in human peripheral blood mononuclear cells, but this effect was neutralized by anti-IFN-beta antibodies.
Conclusions:
- Interferons (IFNs) are the only cytokines possessing intrinsic Mx-inducing activity.
- The observed Mx induction by IL-1, TNF, and IL-2 is mediated indirectly through IFN production.