Recombinant interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells.

Schandené, Liliane; Prete, G.; Cogan, Elie; Stordeur, Patrick; Crusiaux, Alain; Kennès, Bernard; Romagnani, Sergio; Goldman, Michel

doi:10.1172/jci118417

Cited by 141 publications

(86 citation statements)

References 37 publications

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“…Many IFN-α responders reported in the literature present a number of features suggestive of myeloproliferative disease, but these reports pre-date description of F/P-associated disease and L-HES. A corticosteroid-sparing effect of IFN-α has been observed in two of our patients with CD3 -CD4 + clones, which could be related to inhibition of IL-5 production [43] and antiproliferative effects. However, these encouraging results are challenged by the observation that IFN-α prolongs survival of clonal CD3 -CD4 + cells in vitro by inhibiting spontaneous apoptosis, and may therefore provide these cells with a selective advantage [44].…”

Section: F/p-negative Hessupporting

confidence: 53%

Hypereosinophilic Syndromes

Roufosse¹,

Goldman²,

Cogan³

2009

Urticaria and Angioedema, Second Edition

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Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 × 10 9 /L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4-9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato-and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P + variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3 -CD4 + phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P + patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells.

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Section: F/p-negative Hessupporting

confidence: 53%

Hypereosinophilic Syndromes

Roufosse¹,

Goldman²,

Cogan³

2009

Urticaria and Angioedema, Second Edition

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“…However, increasing evidence suggest that IL-10 also acts as an inhibitor of Th2 cell responses both in vitro and in vivo (23)(24)(25). In particular, IL-10 was found to down-regulate IL-5 production by human resting T cells and in human Th0 and Th2 clones (25,26). The inhibitory action of IL-10 on IL-5 synthesis was confirmed in a murine model of allergic eosinophilic peritonitis and airway eosinophilia in which IL-10 administration suppressed both IL-5 production and eosinophil recruitment (24,25).…”

Section: Discussionmentioning

confidence: 99%

T Regulatory Cells 1 Inhibit a Th2-Specific Response In Vivo

Cottrez

Hurst²,

Coffman³

et al. 2000

The Journal of Immunology

327

206

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We recently described a new population of CD4+ regulatory T cells (Tr1) that inhibits proliferative responses of bystander T cells and prevents colitis induction in vivo through the secretion of IL-10. IL-10, which had been primarily described as a Th2-specific cytokine inhibiting Th1 responses, has displayed in several models a more general immune suppression on both types of effector T cell responses. Using an immediate hypersensitivity model in which BALB/c mice immunized with OVA (alum) normally generate Th2-dominated responses, we examined the ability of OVA-specific Tr1 T cell clones to inhibit OVA-specific cytokines and Ab responses. In contrast to Th2 or Th1 T cell clones, transfer of Tr1 T cell clones coincident with OVA immunization inhibited Ag-specific serum IgE responses, whereas IgG1 and IgG2a synthesis were not affected. This specific inhibition was mediated in part through IL-10 secretion as anti-IL-10 receptor Abs treatment reverted the inhibitory effect of Tr1 T cell clones. Although specifically targeted to IgE responses, Tr1 clones’ inhibitory effects were more profound as they affected Ag-specific Th2 cell priming both in term of proliferative responses and cytokine secretion. These results suggest that regulatory T cells may play a fundamental role in maintaining the balance of the immune system to prevent allergic disorders.

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“…32 The mechanisms that control and regulate IL-10 production are still unclear. Some studies report the up-regulation of IL-10 production by substance P, 33 IFN-␣, 34 and IFN-␤. 35 It is of interest that the mouse IL-10 gene has shown regulatory motifs in the enhancer region similar to that in the IL-6 enhancer region because tacrolimus has been shown to enhance IL-6 production in human monocytes.…”

Section: Discussionmentioning

confidence: 99%

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

et al. 2000

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Immunosuppressive therapy has many adverse effects in both the short and longer term. Tailoring immunosuppression might be possible if pretransplantation parameters predicted rejection. We investigated production of the proinflammatory cytokine, tumor necrosis factor-␣ (TNF-␣), and the anti-inflammatory cytokine, interleukin-10 (IL-10), pretransplantation to determine whether there is a relation with acute rejection. Peripheral-blood mononuclear cells were obtained from patients with chronic liver disease on the waiting list for orthotopic liver transplantation and healthy controls. Cells (0.5 ؋ 10 6 ) were stimulated with 200 ng of lipopolysaccharide. Preincubation for 30 minutes with tacrolimus, cyclosporine, and dexamethasone at concentrations of 10 and 100 ng was also performed. TNF-␣ and IL-10 levels were measured by enzyme-linked immunosorbent assay. Acute rejection was defined on clinical and histological grounds. Pretransplantation in vitro production of TNF-␣ significantly (P < .05) increased in the group of patients with acute rejection (n ‫؍‬ 9) compared with those who did not develop rejection (n ‫؍‬ 12). Preincubation with dexamethasone significantly (P < .001) reduced TNF-␣ and IL-10 production in both patients and controls (n ‫؍‬ 8). IL-10 production pretransplantation was not different in those who developed acute rejection (n ‫؍‬ 9) compared with those who did not (n ‫؍‬ 9). Preincubation with tacrolimus augmented (P < .05) the production of IL-10 in patients (n ‫؍‬ 18), but not controls (n ‫؍‬ 6). Pretransplantation TNF-␣ production is increased in patients who go on to develop acute rejection posttransplantion. (Liver Transpl 2000;6:721-727.)

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Recombinant interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells.

Abstract: The effects of recombinant IFN-␣ on the production of IL-5 by human CD4 ؉ T cells were first analyzed on resting CD4

Cited by 141 publications

References 37 publications

Hypereosinophilic Syndromes

Hypereosinophilic Syndromes

T Regulatory Cells 1 Inhibit a Th2-Specific Response In Vivo

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

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