Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation in vitro
Hepatology, 28(6), 1518-1524 · 1998 · doi:10.1002/hep.510280611
Cited by 160+ (per Google Scholar, Aug 2026 — check live count)
Plain-language summary
This laboratory study looked at the cells responsible for liver scarring (fibrosis) — hepatic stellate cells — and the liver's resident immune cells, Kupffer cells (macrophages). Using isolated rat and mouse liver cells, the team discovered something not previously recognised: as stellate cells activate and begin laying down the scar tissue that drives fibrosis, they also start manufacturing interleukin-10 (IL-10), a powerful anti-inflammatory signalling molecule usually associated with immune cells rather than connective-tissue-forming cells. IL-10 production rose steadily as the cells activated in culture, reaching essentially all cells by two weeks, and fluid taken from these activated cells was shown to dampen down inflammatory signalling in macrophages.
Why this matters
This was one of the first papers to show that the cell driving liver scarring isn't just a passive contributor to fibrosis — it actively signals back to the immune system through a well-characterised anti-inflammatory cytokine, pointing to a built-in brake on liver inflammation. That idea helped shape two decades of subsequent research into stellate cell–macrophage crosstalk as a target for anti-fibrotic therapy, which is likely part of why this early-career paper has gone on to accumulate over 160 citations.
Published abstract
Activation of local tissue macrophages (Kupffer cells) and of quiescent hepatic stellate cells (HSCs) to a myofibroblast phenotype are two key events in liver inflammation and fibrosis. It is known that products of activated macrophages may activate stellate cells. We have hypothesized that the products of activated HSCs may also modulate the activity of Kupffer cells. The cytokine interleukin-10 (IL-10), produced by lymphocytes and macrophages, has profound inhibitory actions on macrophages. Normal rat and mouse HSCs that differentiate in vivo and in vitro to activated myofibroblasts were isolated and studied. Conditioned media and lysates from these cells were found to down-regulate lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) secretion by the mouse macrophage line RAW 267.4. In highly purified preparations of rat HSCs, messenger RNA (mRNA) for IL-10 was detected by reverse-transcription polymerase chain reaction (RT-PCR), from the time of isolation to up to 120 days of culture on plastic. Long-term cultures of unstimulated mouse HSCs secreted IL-10 protein as detected by immunoblotting and specific enzyme-linked immunosorbent assay (ELISA). The percentage of IL-10–positive cells increased to 45% at day 7 and 100% by day 14, with expression continuing in long-term cultures of up to 120 days.
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Keywords
hepatic stellate cells interleukin-10 liver fibrosis Kupffer cells macrophages
Cite this publication
Thompson KC, Trowern A, Fowell A, Marathe M, Haycock C, Arthur MJP, Sheron N. Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation in vitro. Hepatology. 1998;28(6):1518-1524. doi:10.1002/hep.510280611Copied!