Disease relevance of IL-5

• Mature pig IL-5 was expressed in Escherichia coli with a His-tag for purification [1].
• An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels [2].
• Neurogenic inflammation, which is mediated by nonadrenergic noncholinergic nerves (NANC), may play a role in the IL-5-induced effects in guinea pig airways [3].
• These studies demonstrate the importance of IL-5 to pulmonary eosinophilia in challenged, allergic guinea pigs [4].
• From these results, it is concluded that IL-5, IL-8 and RANTES, different from PAF and LTB4, are not potent stimuli for the eosinophil chemotaxis and that apafant is a selective antagonist of PAF, which is expected to be therapeutically effective for PAF-associated diseases including bronchial asthma [5].

High impact information on IL-5

• This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity [6].
• Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system [7].
• In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002 [7].
• Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig [8].
• The production of the mRNA was prominently increased when EoL-1 cells were treated with granulocyte macrophage colony stimulating factor, interleukin-5, and n-butyrate [9].

Chemical compound and disease context of IL-5

• Pretreatment with the rat anti-mouse antibody to interleukin-5 (IL-5), TRFK-5 (10-300 microg, intraperitoneally), produced dose-related inhibition of LTD4-induced eosinophilia, measured in 24 h or 3 wk BAL, but did not affect the acute bronchoconstriction [10].
• Data demonstrate that IL-5 is involved in airway eosinophilia, development of LAR and an increase in bronchial responsiveness induced by allergen sensitization via the airways [11].
• Dexamethasone was a potent inhibitor of PAF- induced eosinophil accumulation, but higher doses of dexamethasone were required to inhibit IL-5-induced eosinophilia [12].

Biological context of IL-5

• The full-length pig IL-5 cDNA is 405 base pairs long [1].
• The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs [13].
• Both IL-5/heparin binding and the synergistic effect of IL-5 and heparan sulfate on cell proliferation were inhibited by an anti-IL-5 monoclonal antibody [14].
• Total and differential cell counts of eosinophils and neutrophils were performed on BALF and levels of IL-5 and IL-8 determined by scintillation proximity assays and ELISA, respectively [15].
• The expressions of NF-kappa B, IL-4 and IL-5 mRNA and protein, the proliferation and apoptosis of T lymphocytes were observed by immunohistochemistry, in situ hybridization, ELISA, MTT and TUNEL, respectively [16].

Anatomical context of IL-5

• We show that at low IL-5 concentrations heparan sulfate enhances the proliferation of an IL-5-dependent cell line [14].
• Temporal relationships between leukocytes, IL-5 and IL-8 in guinea pig lungs, plasma cortisol and airway function after antigen challenge [15].
• Inhibition of PAF-, LPS-, and cytokine-induced granulocyte accumulation in guinea pig lung by dexamethasone: evidence that inhibition of IL-5 release is responsible for the selective inhibition of eosinophilia by glucocorticoids in guinea-pigs [12].
• Incubation of bronchial segments with IL-5 potentiated the contractile responses of bronchial smooth muscles to histamine in both intact and sensitized animals [17].
• Contractile responses to histamine on guinea pig trachea and lung parenchyma as well as the release of histamine and interleukin-5 by the tissues were investigated in the absence or presence of levocabastine and/or the histamine H2 receptor antagonist cimetidine [18].

Associations of IL-5 with chemical compounds

• Pig IL-5 was cloned, sequenced, and expressed to enable us to study of the biological role of IL-5 in pigs used in a model for allergen-induced late-phase reactions [1].
• In contrast, an alpha4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5 [7].
• The maximal responses to histamine are increased by 160 +/- 16% (p < 0.05) after IL-5 [3].
• These results indicate that LTD4 elicits airway eosinophil influx in guinea pigs which persists as long as 4 wk after a single exposure, and provide the first evidence that IL-5 may have a role in LTD4-induced airways inflammation [10].
• Treatment of guinea pigs with either the nonselective neurokinin (NK)-receptor antagonist, FK224, or the selective NK2-receptor antagonist, SR48968, results in a complete inhibition of the in vivo hyperresponsiveness found after application of IL-5 [3].

Other interactions of IL-5

• After EA challenge, mRNA expression of interleukin (IL)-5, eotaxin and IL-1beta in BALF cells and IL-5 in the lung increased significantly [19].
• A single CS exposure did not induce obvious inflammatory cell infiltration into the lungs, but it led to significant increases in the mRNA expression of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-8, and monocyte chemoattractant protein (MCP)-1, and decreases in IL-5 and granulocyte-macrophage colony-stimulating factor [20].
• Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SP [21].
• CONCLUSIONS: NF-kappa B may participate in the signal conduction of PKC regulated proliferation, apoptosis and expression of IL-4 and IL-5 of T lymphocytes in asthma [16].
• Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo [8].

Analytical, diagnostic and therapeutic context of IL-5

• Molecular cloning, expression, and purification of pig interleukin-5 [1].
• Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow [7].
• Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5 [7].
• In guinea pigs treated with anti-IL-5, viral infection significantly increased the numbers of eosinophils (234%), neutrophils (1,255%), and monocytes (617%) in bronchoalveolar lavage fluid [22].
• In situ hybridization revealed that challenge-induced increases in IL-5 mRNA-positive cells in lung tissue were significantly inhibited after treatment [13].

References