Effect of Anti-IL-5 and IL-5 on Airway Hyperreactivity and Eosinophils in Guinea Pigs

Abstract

Chronic ovalbumin challenge of sensitized guinea pigs induces bronchoalveolar lavage (BAL) eosinophilia, neutrophilia, and tracheal hyperreactivity. In the present study, the influence of monoclonal antibody to murine interleukin-5 (anti-IL-5) on these phenomena is examined. In ovalbumin-sensitized guinea pigs treated with isotype-matched control antibody and challenged daily with ovalbumin for 8 days, the number of BAL eosinophils and neutrophils is increased significantly six- and fivefold, respectively, compared with saline-challenged animals. The maximal contractions of tracheal rings to histamine and arecoline in ovalbumin-challenged animals are enhanced significantly to 155% compared with saline-challenged animals. In sensitized guinea pigs treated with anti-IL-5, the BAL eosinophil number is markedly inhibited compared with control antibody treatment in both saline- and ovalbumin-challenged animals. In contrast, the number of neutrophils is not affected by anti-IL-5 treatment. In guinea pigs treated with anti-IL-5, the development of hyperreactivity to histamine and arecoline after ovalbumin challenge is completely inhibited. The contractions to histamine and arecoline of tracheal rings isolated from guinea pigs treated with recombinant murine IL-5 for 3 or 7 days are enhanced significantly to approximately 140% compared with controls. Treatment with IL-5 for 7 days tends to increase the number of eosinophils in BAL fluid. It can be concluded that IL-5 is involved in airway eosinophilia and in the development of hyperreactivity in this animal model, but other cytokines may contribute. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthma drugs.

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

“…It is possible that increased serum level of IL-5 may originate from several tissues, including lungs, local lymph nodes, and bone marrow. However, the exact site of action of anti-IL-5 on allergen-induced airway eosinophilia has not been clearly described in several previous studies in which anti-IL-5 was administered systemically (27)(28)(29)(30)(31)(32). A recent study has shown that the anti-IL-5 Ab delivered via the airway route attenuates allergen-induced eosinophilia in BAL and lung tissues (47).…”

Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness.

“…Indeed, IL-5 was present in the BALF and serum of the BP2 mice after antigen challenge and the anti-IL-5 antibody TRFK-5 suppressed altogether eosinophilia in airways and tissues and BHR. In allergen-challenged guinea pigs, anti-IL-5 antibody also suppressed airway eosinophilia (26) and BHR (27,28). CD4+ T lymphocytes that migrate into the lungs after antigen challenge (29) are responsible for the local production of IL-4 and IL-5, which are important in B-and T-lymphocyte development and function and in eosinophil activation and differentiation (30).…”

<i>Justicia procumbens</i> Extract (DW2008) Selectively Suppresses Th2 Cytokines in Splenocytes and Ameliorates Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma

“…4) In other studies, IL-5 and eotaxin were shown as key mediators that facilitate recruitment of eosinophils in the lungs and play pivotal roles in inducing eosinophilic asthma. 5,6) Inhaled corticosteroids (ICSs) and β 2 -agonists have been preferentially used in asthma treatment as controllers and relievers, respectively. However, long-term use of corticosteroids may lead to several adverse effects, including bone fractures and candidiasis, while β 2 -agonists may exacerbate asthma.…”