Recombinant human interleukin 5 is a selective activator of human eosinophil function.

López, Angel F.; Sanderson, Colin J.; Gamble, Jennifer R.; Campbell, Hugh D.; Young, Ian G.; Vadas, Mathew A.

doi:10.1084/jem.167.1.219

Cited by 911 publications

(433 citation statements)

References 20 publications

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“…Increased production of cytokines such as IL-4 by the Th2-like cells is critical in the induction of IgE synthesis and maintenance of established ongoing IgE response [21], and also contributes to the orchestration and perpetuation of the allergic inflammatory process [22,23]. Increased attention has recently turned to the possibility that the clinical efficacy of immunotherapy might be elaborated with alteration of T helper-cell activity and cytokine profiles.…”

Section: Discussionmentioning

confidence: 99%

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

et al. 1998

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Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrolment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

et al. 1998

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“…Therefore, it has been suggested that absence of CD7 defines a CD4 + T cell subset with a Th0/Th2-like cytokine profile. Since IL-5 is another Th2-related cytokine which is produced by T cells exhibiting a Th2 phenotype [14], we evaluated the profile of IL-5 production in CD7 -cells. Here we show that CD4 + CD7 + and CD4 + CD7 -T cells differ in their capacity to secrete distinct cytokines, and the CD4 + CD7 -fraction, particularly, produces high amounts of IL-5 upon activation in vitro.…”

Section: Introductionmentioning

confidence: 99%

The CD7− T cell subset represents the majority of IL-5-secreting cells within CD4+CD45RA− T cells

Reinhold

Liu

Sesterhenn

et al. 1996

Clinical and Experimental Immunology

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SUMMARYAbsence of CD7 is a stable phenotype in a subset of normal human T cells. Most circulating CD7 ÿ T cells express the CD4CD45RO CD45RA ÿ memory phenotype. We analysed CD4 CD45RA ÿ peripheral blood lymphocytes that were separated into CD7 and CD7 ÿ for their in vitro cytokine secretion in response to different stimuli. The CD4 + CD7 -subpopulation was found to secrete significantly higher levels of IL-5 compared with the CD4 + CD7 + subset upon stimulation with ionomycin/phorbol myristate acetate (PMA) plus anti-CD28 MoAbs. In contrast to IL-5 secretion, IL-4 and interferon-gamma (IFN-°) secretion was not significantly different in CD7 and CD7 ÿ T cells upon stimulation in vitro. The data indicate that the CD4 CD7 ÿ T cell represents the majority of IL-5-secreting cells within the population of CD4 CD45RA ÿ memory T cells. Since CD4 CD7 ÿ T cells were found to be enriched in various skin lesions associated with eosinophilic infiltration, the results of our study support the hypothesis that skin-infiltrating CD7 ÿ T cells are one of the major sources of IL-5 responsible for the development of eosinophilic inflammation in certain skin diseases.

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“…The demonstration of eosinophil major basic protein and eosinophil derived neurotoxin indicating degranulation at sites of injury are an important part of the evidence that eosinophils are producing tissue damage in the asthmatic lung (Sur et al 1995). Hence, the current evidence suggests that the local production of IL-5 in asthmatic airways may play an important role in the priming of eosinophils for subsequent activation, and in enhancing their survival at sites of allergic inflammation (Lopez et al 1988, Yamaguchi et al 1988, all of which is likely to be important in asthma.…”

Section: Asthma and Il-5 Human Studies: Il5 Mrna And Proteinmentioning

confidence: 94%

“…It activates mature eosinophils and prolongs their survival in culture (Yamaguchi et al 1988)-possibly via its ability to delay apoptosis , as well as selectively enhancing eosinophil degranulation, antibody-dependent cytotoxicity and adhesion to vascular endothelium (Lopez et al 1988, Fujisawa et al 1990). IL-5 enhances the capacity of eosinophils to release LTC4 (Weller et al 1992) and also primes basophils, leading to increased histamine and LTC4 generation (Bischoff et al 1990, Laviollette et al 1995 and increases synthesis of IgM, IgA, IgE by B cells costimulated with IL-4 (Pene et al 1988, Purkerson & Isakson 1992.…”

Section: Il-5 T Cells and Eosinophilsmentioning

confidence: 99%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

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Recombinant human interleukin 5 is a selective activator of human eosinophil function.

Abstract: Human rIL-5 was found to selectively stimulate morphological changes and the function of human eosinophils. This molecule is thus a prime candidate for the selective eosinophilia and eosinophil activation seen in disease.

Cited by 911 publications

References 20 publications

The CD7− T cell subset represents the majority of IL-5-secreting cells within CD4+CD45RA− T cells

IL-5 and IL-5 receptor in asthma

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