Interleukin‐6 is the major regulator of acute phase protein synthesis in adult human hepatocytes

Castell, José V.; Gómez-Lechón, Marı́a José; David, Martina; Andus, Tilo; Geiger, Thomas; Trullenque, Ramón; Fabra, Ricardo; Heinrich, Peter C.

doi:10.1016/0014-5793(89)80476-4

Cited by 817 publications

(471 citation statements)

References 12 publications

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“…Further major sources of Il-6 may be surrounding fibroblasts or endothelial cells (Kishimoto, 1989). In vivo, CRP reflects Il-6 secretion (Klein et al, 1991) supported by high correlation between serum CRP and Il-6 concentrations in melanoma patients (Moshage et al, 1988;Castell et al, 1989;Kishimoto, 1989;Klein et al, 1991;Hirano, 1992;Tartour et al, 1996;Deichmann et al, 2000).…”

Section: Discussionmentioning

confidence: 98%

“…In line with this report, we previously observed high CRP levels to indicate progression of distant metastases during therapy (Deichmann et al, 2000). As a nonspecific acute phase response to almost all forms of inflammation (Pepys, 1995), CRP is synthesised in hepatocytes in response to cytokines such as mainly interleukin-6 (Il-6; Moshage et al, 1988;Castell et al, 1989;Kishimoto, 1989;Klein et al, 1991;Hirano, 1992). As melanoma cells are known to produce Il-6 (Colombo et al, 1992;Lee et al, 1992;Lu and Kerbel 1993;Mattei et al, 1994;Francis et al, 1996), serum CRP might reflect Il-6 production from the tumour.…”

Section: Discussionmentioning

confidence: 99%

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Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

et al. 2004

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Lactate dehydrogenase (LDH) in serum has recently been introduced into the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma because of its prognostic value. We hypothesised LDH to be of value in discriminating melanoma patients entering AJCC stage IV from patients staying in AJCC stages I, II or III. Lactate dehydrogenase was compared to the acute phase protein C-reactive protein (CRP), which we observed to reflect the course of melanoma metastasis in a previous report. In this prospective study, we measured LDH and CRP in the serum of 91 consecutive melanoma patients progressing into AJCC stage IV in comparison to 125 patients staying in AJCC stages I, II or III. Comparing distributions of the parameters by median values and quartiles by Mann -Whitney test, LDH was not significantly elevated in patients entering AJCC stage IV melanoma (P ¼ 0.785), whereas CRP was (Po0.001). Analysing the sensitivity and the specificity jointly by the areas under the receiver operating characteristics curves (ROC-AUC), LDH did not discriminate between the defined groups of patients (AUC ¼ 0.491; 95% confidence interval, 0.410, 0.581), whereas CRP did (AUC ¼ 0.933; 95% confidence interval, 0.900, 0.966; Po0.001). Upon logistic regression analysis to calculate the ROC-AUC values upon the predictive probabilities, LDH provided no additional information to CRP. Choosing a cutoff point of 3.0 mg l À1 , CRP yielded a sensitivity of 0.769 together with a specificity of 0.904 in diagnosing AJCC stage IV entry. Altogether, for first diagnosing AJCC stage IV melanoma, CRP is the superior serum marker when compared to the conventional LDH.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

et al. 2004

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“…However, this potential measurement error is likely to be random in relation to the hypomanic symptoms outcome. Measurement error might also account for failure to detect an association between CRP and hypomanic symptoms, because IL-6 stimulates the acutephase expression of CRP (Castell et al 1989). It is also possible that we failed to exclude all of those children who were acutely unwell on the day of the blood test, or had elevated inflammatory markers due to residual illness.…”

Section: Potential Limitationsmentioning

confidence: 99%

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

Hayes¹,

Khandaker²,

Anderson³

et al. 2017

Psychol. Med.

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Background. There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood.Method. Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361).Results. After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10-2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose-response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03-2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood.Conclusions. Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.

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“…Both LIF and IL-11 share numerous biological effects with IL-6 on different tissues [6][7][8], including stimulation of APP synthesis by hepatoma cells [4,5]. However, results obtained with tumour cells can be difficult to interpret, since they are not always reproducible with human primary hepatocytes [2,9,10].…”

Section: Introductionmentioning

confidence: 99%

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

Gabay

Singwe

Genin³

et al. 1996

Clinical and Experimental Immunology

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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.

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Interleukin‐6 is the major regulator of acute phase protein synthesis in adult human hepatocytes

Cited by 817 publications

References 12 publications

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

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

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