Long-term interleukin-10 presence induces the development of a novel, monocyte-derived cell type

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Abstract
Interleukin (IL)‐10 is one of the most crucial immunoregulatory cytokines. Its short‐term effects have been analysed extensively, but little is known about its long‐term effects. This is of considerable importance, as high systemic IL‐10 levels are present for long periods in patients with persistent viral infections, certain cancers and in critical care patients. Our study investigated the effects of the long‐term presence of IL‐10 on human peripheral blood monocytes. In vitro, IL‐10 treatment of these cells for 7 days induced the development of a novel cell type characterized by unique phenotypical and functional characteristics. These cells showed high HLA‐DR expression and low expression of CD86 and other co‐stimulatory molecules on their surface. The mRNA levels of both HLA‐DR and CD86 were high, but no intracellular accumulation of CD86 protein was observed. With respect to its function, these cells showed strongly diminished tumour necrosis factor‐α production following lipopolysaccharide stimulation, strongly diminished allogenic CD4+ T cell stimulatory capacity, and even induced a hyporesponsive state in CD4+ T cells. The phenotype remained stable despite the removal of IL‐10. In vivo, we found monocytic cells from patients exhibiting this phenotype after long‐term IL‐10 exposure. These results complement our knowledge further about the biological effects of IL‐10 and may provide an explanation for the sustained immunodeficiency in cases of the persistent presence of systemic IL‐10.

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