Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes

https://doi.org/10.1016/j.bbrc.2004.08.145Get rights and content

Abstract

There is increasing evidence that the adipose tissue and immunologic processes are closely linked. The most abundant protein within the adipocyte is adiponectin. Our current work reports that adiponectin has potent immuno-suppressive properties, as it induces the production of the anti-inflammatory mediators IL-10 and IL-1RA in primary human monocytes, monocyte-derived macrophages, and dendritic cells. In addition, adiponectin significantly impaired the production of the pro-inflammatory cytokine IFN-γ in human macrophages. Moreover, adiponectin-treated macrophages exhibit a reduced phagocytotic and allo-stimulatory capacity. However, we could not detect any functional deficits or phenotypic changes in adiponectin-treated monocytes and monocyte-derived DC. In summary, the presented data support the idea that adiponectin might be of critical relevance for cytokine regulation in obesity and fatty liver diseases affecting primarily macrophage functions. This might represent a fundamental link between over-nutrition and an impaired inflammatory immune response.

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Materials and methods

Cell lines. Human THP1 cells were routinely maintained in RPMI-1640 supplemented with 10% FCS.

Preparation of monocytes, macrophages, and dendritic cells. Human monocytes were isolated from peripheral blood. Briefly, mononuclear cells (PBMC) were isolated from freshly collected buffy-coat preparations of whole human blood by Ficoll–Hypaque gradient centrifugation. CD14+ cells were selected by magnetic bead separation (purity >95%).

For the preparation of macrophages CD14+ cells were seeded grown

IL-10 and IL-1RA are induced in adiponectin-treated monocytes

Incubation of primary human monocytes with adiponectin significantly induced the production of the anti-inflammatory cytokines IL-10 and IL-1RA (Figs. 1A and B). In LPS-stimulated cells, the production of IL-10 was further enhanced by adiponectin, whereas the production of IL-1RA decreased in this setting. Adiponectin treatment of the myeloid cell line THP1 resulted in increased IL-1RA levels in both, unstimulated as well as LPS-activated, cells whereas IL-10 was not detectable (data not shown).

Discussion

Our current study demonstrates that the adipokine adiponectin is sufficient to induce the expression of anti-inflammatory cytokines such as IL-10 and IL-1RA in a variety of myeloid cell types, such as monocytes, a myeloid cell line (THP-1), primary human dendritic cells as well as monocyte-derived macrophages. In line with this anti-inflammatory phenotype, adiponectin-treated macrophages are characterized by a reduced production of IFN-γ as well as a limited ability to evoke allogeneic T-cell

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This work was supported by the FWF Grant No. P15783 (to H.T.).

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