Antibody to Interleukin-5 Inhibits Helminth-Induced Eosinophilia in Mice

Coffman, Robert L.; Seymour, Brian W. P.; Hudak, Susan; Jackson, John D.; Rennick, Donna

doi:10.1126/science.2787531

Cited by 586 publications

(329 citation statements)

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“…A llergic immunopathology and host protection against helminth parasites are both mediated, in large part, by the type 2 cytokines IL-4, IL-5, IL-9, and IL-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Of these, a particularly prominent role is played by two related cytokines, IL-4 and IL-13.…”

mentioning

confidence: 99%

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Khodoun

Lewis²,

Yang

et al. 2007

The Journal of Immunology

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IL-4 and IL-13 are each bound by soluble receptors (sRs) that block their activity. Both of these sRs (sIL-4Rα and sIL-13Rα2) are present in low nanogram per milliliter concentrations in the serum from unstimulated mice, but differences in affinity and half-life suggest differences in function. Serum IL-4/sIL-4Rα complexes rapidly dissociate, releasing active IL-4, whereas sIL-13Rα2 and IL-13 form a stable complex that has a considerably longer half-life than uncomplexed IL-13, sIL-13Rα2, IL-4, or sIL-4Rα. Approximately 25% of sIL-13Rα2 in serum is complexed to IL-13; this percentage and the absolute quantity of sIL-13Rα2 in serum increase considerably during a Th2 response. sIL-13Rα2 gene expression is up-regulated by both IL-4 and IL-13; the effect of IL-4 is totally IL-4Rα-dependent while the effect of IL-13 is partially IL-4Rα-independent. Inhalation of an IL-13/sIL-13Rα2 complex does not affect the expression of IL-13-inducible genes but increases the expression of two genes, Vnn1 and Pira-1, whose products activate APCs and promote neutrophilic inflammation. These observations suggest that sIL-4Rα predominantly sustains, increases, and diffuses the effects of IL-4, whereas sIL-13Rα2 limits the direct effects of IL-13 to the site of IL-13 production and forms a stable complex with IL-13 that may modify the quality and intensity of an allergic inflammatory response.

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mentioning

confidence: 99%

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Khodoun

Lewis²,

Yang

et al. 2007

The Journal of Immunology

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“…Many investigators have demonstrated a direct correlation between eosinophilia and IL-5 in human helminth infection and in experimental animal models. It has also been demonstrated that anti-IL-5 mAb treatment inhibits eosinophilia in mice infected with Toxocara canis, Nippostrongylus brasiliensis and Schistosoma mansoni (14)(15)(16). In addition, IL-5 plays an important role in mobilizing eosinophils from bone marrow to peripheral blood and in priming eosinophils to respond easily to other chemotactic stimuli such as chemokines and lipid mediators (7,17).…”

mentioning

confidence: 99%

Interleukin-5 mediates peritoneal eosinophilia induced by the F1 cell wall fraction of Histoplasma capsulatum

Sá-Nunes

Medeiros

Faccioli

2004

Braz J Med Biol Res

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An alkali-insoluble fraction 1 (F1), which contains mainly ß-glucan isolated from the cell wall of Histoplasma capsulatum, induces eosinophil recruitment into the peritoneal cavity of mice. The present study was carried out to determine the participation of interleukin-5 (IL-5) in this process. Inbred C57BL/6 male mice weighing 15-20 g were treated ip with 100 µg of anti-IL-5 monoclonal antibody (TRFK-5, N = 7) or an isotype-matched antibody (N = 7), followed by 300 µg F1 in 1 ml PBS ip 24 h later. Controls (N = 5) received only 1 ml PBS. Two days later, cells from the peritoneal cavity were harvested by injection of 3 ml PBS and total cell counts were determined using diluting fluid in a Neubauer chamber. Differential counts were performed using Rosenfeld-stained cytospin preparations. The F1 injection induced significant (P < 0.01) leukocyte recruitment into the peritoneal cavity (8.4 x 10 6 cells/ml) when compared with PBS alone (5.5 x 10 6 cells/ ml). Moreover, F1 selectively (P < 0.01) induced eosinophil recruitment (1 x 10 6 cells/ml) when compared to the control group (0.07 x 10 6 cells/ml). Treatment with TRFK-5 significantly (P < 0.01) inhibited eosinophil recruitment (0.18 x 10 6 cells/ml) by F1 without affecting recruitment of mononuclear cells or neutrophils. We conclude that the F1 fraction of the cell wall of H. capsulatum induces peritoneal eosinophilia by an IL-5-dependent mechanism. Depletion of this cytokine does not have effect on the recruitment of other cell types induced by F1.

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“…Other allergic pulmonary and non-pulmonary allergic diseases -There is a strong association between IL-5 and eosinophilia in a number of allergic human diseases, including parasitic infections (Coffman et al 1989, Limaye et al 1993, Hagan et al 1996, atopic dermatitis (Frew & Kay 1988, Hamid et al 1994, eosinopilic myocarditis (Desreumaux et al 1993), hypereosinopilic syndrome (Schrezenmeier et al 1993, Satoh et al 1994) eosinophilic gastroenteritis (Quan et al 1993, Dubucquoi et al 1995, allergic rhinitis , chronic eosinophilic pneumonia and other eosinophilic lung diseases (Walker et al 1994) (Fig. 1).…”

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

confidence: 99%

“…However, only IL-5 was selective for the eosinophil lineage (Clutterbuck et al 1989). Transgenic mice which constituitively express IL-5 have high level, lifelong eosinophilia (Dent et al 1990) and the administration of anti-IL-5 neutralising antibody in parasite infected mice totally blocks the production of eosinophilia (Coffman et al 1989.…”

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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Antibody to Interleukin-5 Inhibits Helminth-Induced Eosinophilia in Mice

Cited by 586 publications

References 20 publications

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Interleukin-5 mediates peritoneal eosinophilia induced by the F1 cell wall fraction of Histoplasma capsulatum

IL-5 and IL-5 receptor in asthma

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