Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids.

Abstract

Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-a, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from -1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations ( 1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock. (J. Clin. Invest. 1992. 90:2031-2037

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).…”

“…IL-11 mRNA and protein are expressed in articular chondrocytes and synoviocytes activated in vitro by cytokines such as IL-1 and transforming growth factor p, as detected by Northern blot analysis and immunoprecipitation (21). LIF production by cells in the synovium and cartilage has also been reported by several investigators (22,23), and LIF has been detected at significant levels in synovial fluids from RA patients (24,25). We have shown that cells isolated from the synovium of RA patients spontaneously produce IL-6, IL-11, LIF, and OSM at higher levels than the synovial cells of OA patients.…”

“…Studies of IL-6-deficient mice have also shown that the APP production response after tissue damage with turpentine or Listeria infection is severely compromised, whereas it is only slightly affected when systemically challenged with LPS injection (45). 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).…”

“…More recently, the expression of IL-11 and LIF in synoviocytes and articular chondrocytes has been described (21)(22)(23). 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).…”

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

“…High levels were also found in synovial fluid (SF) from approximately one-quarter of a series of patients with RA and other inflammatory arthritides, but these values did not correlate with clinical or laboratory signs of disease activity [30]. In contrast, serum LIF was detected in only a few patients with septic shock and in none with rheumatic diseases [11]. Accordingly, we could not detect the presence of LIF in any of the sera tested, although most patients had obvious signs of disease activity.…”