Abstract
Interleukin (IL)-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT)-3 as dominant signaling mode. IL-10, formerly known as cytokine synthesis inhibitory factor, is key to deactivation of monocytes/macrophages and dendritic cells. Accordingly, pre-clinical studies document its anti-inflammatory capacity. However, the outcome of clinical trials assessing the therapeutic potential of IL-10 in prototypic inflammatory disorders has been disappointing. In contrast to IL-10, IL-22 acts primarily on non-leukocytic cells, in particular epithelial cells of intestine, skin, liver, and lung. STAT3-driven proliferation, anti-apoptosis, and anti-microbial tissue protection is regarded a principal function of IL-22 at host/environment interfaces. In this hypothesis article, hidden/underappreciated pro-inflammatory characteristics of IL-10 and IL-22 are outlined and related to cellular priming by type I interferon. It is tempting to speculate that an inherent inflammatory potential of IL-10 and IL-22 confines their usage in tissue protective therapy and beyond that determines in some patients efficacy of type I interferon treatment.
Highlights
Type I interferon (IFN), interleukin (IL)-10, and IL-22 are cytokines that accomplish fundamental tasks in tailoring immunoactivation in a broad array of pathophysiological conditions
We investigated effects of IFNα priming on IL22 signal transduction and noted, in similarity to data on IL-10, amplification of IL-22-activated STAT1 in primed cells
Present data suggest that priming by type I IFN is able to target IL-10/IL-22 cellular signaling toward STAT1-driven IFNγ-like activation
Summary
Type I interferon (IFN), interleukin (IL)-10, and IL-22 are cytokines that accomplish fundamental tasks in tailoring immunoactivation in a broad array of pathophysiological conditions. Spotlight will be thrown on specific pro-inflammatory properties of IL-10 and IL-22 that, in the case of IL-10, call attention at second glance, may relate to interactions with type I IFN, and potentially confine usage of both cytokines in tissue protective therapy. Since IL-22 application to healthy mice appears neither be connected to induction of acute inflammation nor to overt immunosuppression as assessed by analysis of basal and endotoxin-induced systemic levels of inflammatory cytokines (Wolk et al, 2004; Scheiermann et al, 2012), current data on the whole suggest short-term usage of this cytokine for tissue protective therapy.
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