Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.

Abstract

SummaryAirways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to [3-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished, l~econstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroaUergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.

A role for MC3R in modulating lung inflammation

“…The cell infiltrate was predominantly monocytic in shamimmunized mice. However, a significant increase in the percentage of eosinophils and lymphocytes was observed in immunized mice following aerosol exposure to ovalbumin, consistent with previous studies in this strain of mice [34]. The allergic inflammatory response to ovalbumin was mildly exacerbated (~25%; not significant) in recessive yellow e/e and MC3R null mouse, indicating that under the present experimental conditions, endogenously released melanocortins might not interfere with the process of allergen sensitisation or to the inflammatory response per se.…”

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

“…In asthma, Th2-related cytokines such as IL-4 [35–37], IL-5 [38], and IL-13 [35,37] significantly increase; the development of antibodies against Th2-related cytokines is an active field of research [39]. Changes in Th17 cells correlate with asthma induction, making it important to analyze Th-17 proteins such as TNF-α, IL-6, and IL-1β [40].…”

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

“…Since previous studies have shown that PD-L2 expression may be regulated in some cell types by Th2 cytokines or Th2 cells [21], and because asthma is believed to be a Th2-driven disease [23][24][25][26][27][28][29][30][31][32], it was of interest to examine whether PD-L2 can play a role in immune regulation in this context.…”

“…Asthma is a chronic disease which can be characterized by airway hyper-responsiveness, mucus hypersecretion by goblet cells, infiltration of the airway wall with leukocytes, and elevation of serum IgE [23 24]. Studies in mouse models have established a critical role for Th2 cells, DC, Treg [24][25][26][27][28], and the Th2 type cytokines IL-4, IL-5, IL-9, and IL-13 in the asthmatic response [23,26,[29][30][31][32]. The role of the PD-1/PD-L1/PD-L2 axis in asthma is currently unknown.…”