Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice.

Kips, Johan; Brusselle, Guy; Joos, Guy; Peleman, Renaat; Tavernier, Jan; Devos, Rr; Pauwels, Romain

doi:10.1164/ajrccm.153.2.8564093

Cited by 186 publications

(124 citation statements)

References 10 publications

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“…IL-12, a well-characterized Th1 cytokine, can reduce airway hyperresponsiveness (27). IL-12 is a heterodimeric cytokine composed of two subunits (p35 and p40).…”

Section: Discussionmentioning

confidence: 99%

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Careau¹,

Proulx²,

Pouliot³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-We have previously demonstrated that adoptive transfer of alveolar macrophages from allergy-resistant rats to alveolar macrophage-depleted allergic rats prevents airway hyperresponsiveness development, suggesting an important role for alveolar macrophages in asthma pathogenesis. Given that ovalbumin sensitization can modulate alveolar macrophage cytokine production, we investigated the role of sensitized and unsensitized alveolar macrophages in an asthma model. Alveolar macrophages from unsensitized or sensitized Brown Norway rats were transferred to alveolar macrophage-depleted sensitized rats 24 h before allergen challenge. Airway responsiveness to methacholine and airway inflammation were measured the following day. Methacholine concentration needed to increase lung resistance by 200% was significantly higher in alveolar macrophage-depleted sensitized rats that received unsensitized alveolar macrophages compared with alveolar macrophage-depleted sensitized rats that received sensitized alveolar macrophages. Tumor necrosis factor levels in bronchoalveolar lavage fluid of sensitized rats that received unsensitized alveolar macrophages were significantly lower compared with rats that received sensitized alveolar macrophages. Interestingly, alveolar macrophages of unsensitized animals showed higher phagocytosis activity compared with alveolar macrophages of sensitized rats, suggesting that sensitization modulates alveolar macrophage phagocytosis function. Our data suggest an important role of allergen sensitization on alveolar macrophage function in asthma pathogenesis. airway hyperresponsiveness; cytokine; phagocytosis THE INCIDENCE OF allergic respiratory diseases increased dramatically over the last two decades. The genetic predisposition to develop asthma is now well recognized (20). Numerous studies have also shown the importance of inflammatory cells, such as mast cells, lymphocytes, eosinophils, and neutrophils, as well as Th2 type cytokines in asthma (6,19,32). Interleukin (IL)-4 and IL-13, two Th2 cytokines, are important in immunoglobulin (Ig) class switching to IgE, whereas IL-4 and IL-10 play a crucial role in Th2 cell commitment (9,16,50). In contrast, Th1 cytokines (interferon-␥ and IL-12) protect against asthma development in children (48). Other cytokines, such as tumor necrosis factor (TNF), have been demonstrated to amplify the effect of asthmatic inflammation (29,42). Recently, a role of regulatory T cells (Th3 cells, T R cells, CD4 ϩ CD25 ϩ cells, and natural killer T cells) has been suggested in the control of asthma and allergy, but the specific mechanisms are still unknown (2).Alveolar macrophages (AM) are predominant immune effector cells in the alveolar spaces and conducting airways and play a key role in the immunological homeostasis of the lung (8, 30, 43). Although they are well known to suppress T cell activation and antigen presentation activities of dendritic cells (22,41), their role in asthma is still debated. Using the liposome-mediated macrophage suicide technique (47), we have...

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“…IL-12, a well-characterized Th1 cytokine, can reduce airway hyperresponsiveness (27). IL-12 is a heterodimeric cytokine composed of two subunits (p35 and p40).…”

Section: Discussionmentioning

confidence: 99%

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Careau¹,

Proulx²,

Pouliot³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In preliminary studies a modification of a commonly adopted protocol used in mouse AHR induction studies was tested (23). Immunization i.t.…”

Section: Priming With Ova-pulsed DC Induced Ahrmentioning

confidence: 99%

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Sung

Rose

2001

The Journal of Immunology

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Dendritic cells (DC) are the primary APC responsible for the capture of allergens in the airways and the shuttling of processed allergens to the draining lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly understood. In addition, the feasibility of asthma induction by DC priming has not been directly tested. In this report an asthma model using intratracheally (i.t.) injected splenic DC was used to address these issues. DC pulsed with a model Ag OVA or the major MHC class II-restricted OVA T epitope peptide OVA323–339 and instilled i.t. primed mice to exhibit asthma-like diseases. With OVA as the Ag, mice exhibit airway hyperresponsiveness (AHR), lung eosinophilia and inflammation, and pulmonary goblet cell hyperplasia. In OVA323–339-immunized mice, AHR and goblet cell hyperplasia were noted, with little eosinophilia and parenchymal inflammation. The latter finding provides evidence for dissociating AHR from eosinophilia. In both cases mediastinal node hypertrophy occurred, and high levels of Th2 cytokines were produced by the lung and mediastinal lymph node cells (LNC). Interestingly, mediastinal LNC also produced high levels of Th1 cytokines. Lung cells produced much less Th1 cytokines than these LNC. These results demonstrate that DC when introduced i.t. are potent in inducing asthma-like diseases by recruiting lymphocytes to the lung-draining lymph nodes and by stimulating Th2 responses and also suggest that the lung environment strongly biases T cell responses to Th2.

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“…10). The beneficial effects of LPS are thought to be mediated by enhanced secretion of the type 1 cytokines IL-12 and IFN-␥ that are known to down-modulate allergic responses (11,12). Conversely, airborne LPS might adversely affect asthmatics by enhancing an established airway inflammation and airway obstruction (13,14).…”

mentioning

confidence: 99%

Bacterial Lipopolysaccharide Signaling Through Toll-Like Receptor 4 Suppresses Asthma-Like Responses Via Nitric Oxide Synthase 2 Activity

Rodríguez

Keller

Faquim-Mauro

et al. 2003

The Journal of Immunology

152

153

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Asthma results from an intrapulmonary allergen-driven Th2 response and is characterized by intermittent airway obstruction, airway hyperreactivity, and airway inflammation. An inverse association between allergic asthma and microbial infections has been observed. Microbial infections could prevent allergic responses by inducing the secretion of the type 1 cytokines, IL-12 and IFN-γ. In this study, we examined whether administration of bacterial LPS, a prototypic bacterial product that activates innate immune cells via the Toll-like receptor 4 (TLR4) could suppress early and late allergic responses in a murine model of asthma. We report that LPS administration suppresses the IgE-mediated and mast cell-dependent passive cutaneous anaphylaxis, pulmonary inflammation, airway eosinophilia, mucus production, and airway hyperactivity. The suppression of asthma-like responses was not due to Th1 shift as it persisted in IL-12−/− or IFN-γ−/− mice. However, the suppressive effect of LPS was not observed in TLR4- or NO synthase 2-deficient mice. Our findings demonstrate, for the first time, that LPS suppresses Th2 responses in vivo via the TLR4-dependent pathway that triggers NO synthase 2 activity.

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Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice.

Cited by 186 publications

References 10 publications

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Bacterial Lipopolysaccharide Signaling Through Toll-Like Receptor 4 Suppresses Asthma-Like Responses Via Nitric Oxide Synthase 2 Activity

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