Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys

Jelkmann, Wolfgang; Pagel, Horst; Wolff, Martin; Fandrey, Joachim

doi:10.1016/0024-3205(92)90338-p

Cited by 200 publications

(101 citation statements)

References 25 publications

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“…Interestingly, we also show that TNF and IFN-γ inhibit EPO expression in neuronal and glial cell, in agreement with previous reports showing an inhibitory effect of inflammatory cytokines on EPO expression outside the CNS (41). These data, together with the known inhibitory effect of EPO on neuroinflammation (3,6), reveal a cross-talk between EPO and inflammatory cytokines in the CNS, outlined in Figure 6.…”

Section: Discussionsupporting

confidence: 92%

Endogenous Erythropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Mengozzi

Cervellini

Bigini

et al. 2008

Mol Med

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Erythropoietin (EPO) is of great interest as a therapy for many of the central nervous system (CNS) diseases and its administration is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Endogenous EPO is induced by hypoxic/ischemic injury, but little is known about its expression in other CNS diseases. We report here that EPO expression in the spinal cord is induced in mouse models of chronic or relapsing-remitting EAE, and is prominently localized to motoneurons. We found a parallel increase of hypoxia-inducible transcription factor (HIF)-1α, but not HIF-2α, at the mRNA level, suggesting a possible role of non-hypoxic factors in EPO induction. EPO mRNA in the spinal cord was co-expressed with interferon (IFN)-γ and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glial cells. Given the known inhibitory effect of EPO on neuroinflammation, our study indicates that EPO should be viewed as part of the inflammatory/anti-inflammatory network in MS.

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Section: Discussionsupporting

confidence: 92%

Endogenous Erythropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Mengozzi

Cervellini

Bigini

et al. 2008

Mol Med

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“…Cytokines such as IL-1 and TNF-␣ activate GATA-2 and NF-B, suggesting that both transcription factors are involved in the inhibition of Epo gene expression in inflammatory diseases (85,103). In vitro, proinflammatory cytokines such as IL-1␣, IL-1␤, and TNF-␣ dose dependently inhibit hypoxia-induced Epo gene mRNA, and protein expression (50,88). In chronic diseases, anemia is seen together with enhanced IFN-␥, IL-1, and TNF-␣ (109).…”

Section: Regulation Of Epo Productionmentioning

confidence: 99%

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Jie

Verhaar²,

Cramer³

et al. 2006

American Journal of Physiology-Renal Physiology

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We have recently proposed severe cardiorenal syndrome (SCRS), in which cardiac and renal failure mutually amplify progressive failure of both organs. This frequent pathophysiological condition has an extremely poor prognosis. Interactions between inflammation, the renin-angiotensin system, the balance between the nitric oxide and reactive oxygen species and the sympathetic nervous system form the cardiorenal connectors and are cornerstones in the pathophysiology of SCRS. An absolute deficit of erythropoietin (Epo) and decreased sensitivity to Epo in this syndrome both contribute to the development of anemia, which is more pronounced than renal anemia in the absence of heart failure. Besides expression on erythroid progenitor cells, Epo receptors are present in the heart, kidney, and vascular system, in which activation results in antiapoptosis, proliferation, and possibly antioxidation and anti-inflammation. Interestingly, Epo can improve cardiac and renal function. We have therefore reviewed the literature with respect to Epo and the cardiorenal connectors. Indeed, there are indications that Epo can diminish inflammation, reduce renin-angiotensin system activity, and shift the nitric oxide and reactive oxygen species balance toward nitric oxide. Information about Epo and the sympathetic nervous system is scarce. This analysis underscores the relevance of a further understanding of clinical and cellular mechanisms underlying protective effects of Epo, because this will support better treatment of SCRS. heart failure; renal failure; anemia; nitric oxide; reactive oxygen species COEXISTENCE OF RENAL AND cardiac disease is associated with high morbidity and mortality. This pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has recently been denoted as severe cardiorenal syndrome (SCRS) (19,20).In patients with declined renal function measured by glomerular filtration rate (GFR), an independent increased risk for cardiovascular events has been found. The hazard ratio for cardiovascular events was 1.4 with a GFR Ͻ60 ml/min and increased with diminished renal function to 2.8 in patients with a GFR Ͻ30 ml/min (99). A 40% higher adjusted risk for adverse cardiovascular outcomes or death was observed in those with relatively minor degrees of renal dysfunction (120). The prevalence of chronic renal failure (CRF) is reportedly high in patients with congestive heart failure (CHF). Furthermore, the prevalence and severity of CRF correlate with the severity of CHF (44, 72). These data support that combined cardiac and renal failure is a profound problem, and a further understanding of the underlying pathophysiological and molecular mechanisms is needed to improve therapy.Our group proposed an interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide and reactive oxygen species (NO-ROS) balance, the sympathetic nervous system (SNS), and inflammation, as the cornerstones of the pathophysiology o...

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“…When inflammation occurs, Epo levels fall further, with in vitro evidence supporting that inflammatory cytokines inhibit Epo production. 58,59 In a retrospective review, infants treated with recombinant human (rh)Epo experience a lower incidence of NEC, compared to placebo. 20 Epo receptors are present on gastrointestinal epithelial cells, with studies supporting physiologic effects.…”

Section: Anemia Pathophysiology Of Anemiamentioning

confidence: 99%

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

Kling

Hutter

2003

J Perinatol

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Necrotizing enterocolitis (NEC), the most common surgical emergency in newborns, remains a therapeutic challenge for clinicians. The hematological manifestations associated with NEC were first described 25 years ago. This review discusses current knowledge of the pathophysiology involved in disturbances in megakaryocytopoiesis, coagulation, leukopoiesis, and erythropoiesis that accompany the clinical entity NEC. The discussion includes current understanding of and potential strategies for treating the hematopoietic disturbances that occur secondary to NEC.

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Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys

Cited by 200 publications

References 25 publications

Endogenous Erythropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Endogenous Erythropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

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