Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver

Abstract

SUMMARYTo investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.

The synovial expression and serum levels of interleukin‐6, interleukin‐11, leukemia inhibitory factor, and oncostatin m in rheumatoid arthritis

“…However, the transport of such mediators to the liver is most critical in this process. Circulating levels of IL-11 and LIF have previously been reported as being undetectable in RA patients (24,26). We failed to detect serum OSM as well as these 2 cytokines in RA patients, but found that only IL-6 was markedly elevated and correlated with serum CRP levels, which is consistent with previous results (19).…”

“…In this regard, markedly elevated concentrations of LIF have been detected only in the serum of patients with septic shock and severe tissue damage (24). More importantly, a recent study of human primary hepatocytes has shown that the effects of IL-11 and LIF on hepatocyte APP production were limited compared with the effect of IL-6 (26). Therefore, despite a functional redundancy of IL-6-type cytokines, IL-6 may be a predominant mediator of the acute-phase response when inflammation and tissue damage are localized.…”

“…LJF has been found at high levels in synovial fluids from patients with inflammatory arthritides such as RA (22,24,25). However, IL-11 and LIF have been reported to be undetectable in the circulation of RA patients (24,26).…”

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

“…The function of the APP is to control body homeostasis and to regulate the inflammatory reaction. Many neuropoietic cytokines stimulate the release of APP from cultured hepatocytes [8][9][10][11][12], while IL-6 appears to be a primary inducer of APP in vivo [13][14][15]. The acute phase reaction elicited by infection or tissue damage is drastically reduced in IL-6 knockout (KO) mice, while lipopolysaccharide (LPS)-triggered APP secretion is only slightly diminished in these mice [16][17][18].…”

True

“…6,38 It has also been concluded that circulating levels of IL-11 do not contribute to a major extent to liver acute phase protein production. 39 IL-11 has been found in synovial fluid and in human ovarian follicular fluid. 7 The function of IL-11 in these compartments has been linked to its anti-inflammatory activity and involvement in follicular maturation.…”