Interleukin 4 inhibits the production of some acute‐phase proteins by human hepatocytes in primary culture

Loyer, Pascal; Ilyin, Gennady; Razzak, Ziad Abdel; Banchereau, Jacques; Dezier, Jean‐François; Campion, Jean‐Pierre; Guguen‐Guillouzo, Christiane; Guillouzo, André

doi:10.1016/0014-5793(93)80806-6

Cited by 59 publications

(32 citation statements)

References 34 publications

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“…Support for this view is provided by the finding that the addition of IL-4 to cultures of primary human hepatocytes increases the production of GST (58). The responsiveness of hepatocytes to IL-4 is also indicated by the finding that the cytokine inhibits lipogenesis stimulated by IL-1, IL-6, and TNF-␣ in murine hepatocytes (59). Because the production of all Th2 cytokines is dramatically reduced, and the production of the inflammatory cytokines (e.g., IFN-␥ and TNF-␣) is increased during infection in IL-4 Ϫ/Ϫ mice (3,10), it is also probable that differences in the levels of other cytokines may be influencing the production of catalase and SOD in the liver (60 -62).…”

Section: Discussionmentioning

confidence: 49%

IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis

Flamme

Patton

Bauman

et al. 2001

The Journal of Immunology

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Liver enlargement and hepatocyte proliferation, normal responses in wild-type (WT) mice infected with the parasitic helminth Schistosoma mansoni, were found to be severely impaired in infected IL-4−/− mice. Compared with WT mice, increased levels of O2−, NO, and the more highly reactive ONOO− were detected in the liver and produced by lesional cells isolated from liver granulomas of infected IL-4−/− mice. Concurrently, antioxidant defenses in the liver, specifically catalase levels, diminished dramatically during the course of infection in these animals. This contrasted to the situation in infected WT mice, where catalase levels remained as high as those in normal mice. Actual levels of reactive oxygen and nitrogen intermediates in the livers of infected IL-4−/− animals are thus likely to be considerably higher than those in the livers of infected WT mice. To determine whether these changes contributed to the development of the more severe disease that characterizes infection in the IL-4−/− animals, we treated infected IL-4−/− mice with uric acid, a potent scavenger of ONOO−. This resulted in significantly increased hepatocyte proliferation, decreased morbidity, and prolonged survival. Taken together, these data indicate that IL-4 is playing a protective role during schistosomiasis by controlling the tight regulation of the generation of reactive oxygen and nitrogen intermediates in the liver.

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Section: Discussionmentioning

confidence: 49%

IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis

Flamme

Patton

Bauman

et al. 2001

The Journal of Immunology

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“…Cytokines were chosen according to known effects on either CYP expression or acute phase protein production by human and rodent hepatocyte primary cultures [4,9,20,21]. No apparent cytotoxicity was observed in response to the cytokines alone or in combination with the inducers.…”

Section: Resultsmentioning

confidence: 99%

“…The cytokines have previously been found to regulate basal cytochrome P, s0 expression in primary cultured human hepatocytes [4,9] and/or acute-phase protein expression in both rat and human hepatocytes in primary culture [20,21], At concentrations used none of th~ cytokines induced mot'phological alterations. 3-MC was dissolved in DMSO and was added at the concentration of 5 juM which was found to ~ optimal for induction of EROD activity, although quite as strong an induction was observed for 0.5,uM.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

Interleukin‐1β antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

et al. 1995

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“…The ELISA procedure used to measure the concentrations of haptoglobin was adapted from a previously described method [23]. Plates were coated with goat anti-haptoglobin antibodies and culture supernatants were added to the wells.…”

Section: Elisa For Haptoglobinmentioning

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 4 inhibits the production of some acute‐phase proteins by human hepatocytes in primary culture

Cited by 59 publications

References 34 publications

IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis

IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis

Interleukin‐1β antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

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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