Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

doi:10.1016/j.jaci.2006.04.021

Journal of Allergy and Clinical Immunology

Volume 118, Issue 2, August 2006, Pages 389-395

https://doi.org/10.1016/j.jaci.2006.04.021 Get rights and content

Background

Epidemiologic data indicate an increased incidence of asthma in the obese.

Objective

Because serum levels of the insulin-sensitizing and anti-inflammatory adipokine adiponectin are reduced in obese individuals, we sought to determine whether exogenous adiponectin can attenuate allergic airway responses.

Methods

We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet micro-osmotic pumps were implanted in the mice to deliver continuous infusions of buffer or adiponectin (1.0 μg/g/d), which resulted in an approximate 60% increase in serum adiponectin levels. Two days later, mice were challenged with aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours after the last challenge.

Results

OVA challenge increased airway responsiveness to intravenous methacholine, bronchoalveolar lavage fluid cells, and T_H2 cytokine levels. Importantly, each of these responses to OVA was reduced in adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in serum adiponectin levels and a corresponding decrease in adipose tissue adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA expression of each of 3 proposed adiponectin-binding proteins, adiponectin receptor 1, adiponectin receptor 2, and T-cadherin.

Conclusion

Our results indicate that serum adiponectin is reduced during pulmonary allergic reactions and that adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice.

Clinical implications

The data suggest that adiponectin might play a role in the relationship between obesity and asthma.

Section snippets

Allergen sensitization and challenge

This study was approved by the Harvard Medical Area Standing Committee on Animals. Male and female 4-week-old BALB/cJ mice were purchased from The Jackson Laboratory (Bar Harbor, Me). Mice were sensitized to chicken egg albumin (ovalbumin [OVA]; Grade V, Sigma-Aldrich, St Louis, Mo) on day 0 by means of an intraperitoneal injection of 20 μg of OVA and adjuvant and 2 mg of aluminum hydroxide (Al[OH]₃; J. T. Baker, Phillipsburg, NJ) dispersed in 0.2 mL of PBS, as previously described.⁴⁴ The mice

Body weight

There was a small reduction in body weight the day after implantation of the mini-Alzet pumps that averaged 2.3% ± 0.6% of the initial body weight. Body weight recovered to baseline values by the day of the first OVA/PBS aerosol challenge in both TBS- and adiponectin-treated mice. There was no significant effect of either OVA/PBS challenge or adiponectin versus TBS treatment on body weight.

BAL cells and cytokines

Compared with PBS challenge, OVA challenge caused a significant increase in BAL macrophages (P < .05),

Discussion

Our results indicate for the first time that treatment of mice with full-length adiponectin at a dose sufficient to induce an approximate 60% increase in serum adiponectin levels virtually abolishes OVA-induced changes in inflammatory cell influx (Fig 1) and T_H2 cytokine expression in the lungs (Fig 2), as well as OVA-induced airway hyperresponsiveness (Fig 3). Obesity is associated with decreases in serum adiponectin levels that are on the same order of magnitude as the increase in serum

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Supported by National Institutes of Health grants HL33009 and HL077499, National Institute of Environmental Health Sciences grants ES013307 and ES00002, a generous gift from Paul and Mary Finnegan, and a Charles H. Hood Foundation grant.

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

View full text

Mechanisms of asthma and allergic inflammationAdiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Allergen sensitization and challenge

Body weight

BAL cells and cytokines

Discussion

J Allergy Clin Immunol

Pharmacol Ther

Chest

Chest

Chest

J Allergy Clin Immunol

J Biol Chem

Curr Opin Pharmacol

Blood

Biochem Biophys Res Commun

Biochem Biophys Res Commun

Biochem Biophys Res Commun

Biochem Biophys Res Commun

FEBS Lett

J Allergy Clin Immunol

J Biol Chem

Biochem Biophys Res Commun

Prospective study of body mass index, weight change, and risk of adult-onset asthma in women

Arch Intern Med

Body mass index in relation to adult asthma among 135,000 Norwegian men and women

Am J Epidemiol

Body-mass index as a predictor of incident asthma in a prospective cohort of children

Pediatr Pulmonol

Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years

Am J Respir Crit Care Med

Relation of bronchial responsiveness to body mass index in the ECRHS

European Community Respiratory Health Survey. Thorax

Body mass index and asthma in adults in families of subjects with asthma in Anqing, China

Am J Respir Crit Care Med

Responses to ozone are increased in obese mice

J Appl Physiol

Differential effects of ozone on airway and tissue mechanics in obese mice

J Appl Physiol

Augmented Responses to ozone in obese carboxypeptidase E-deficient mice

Am J Physiol Regul Integr Comp Physiol

Increased pulmonary responses to acute ozone exposure in obese db/db mice

Am J Physiol Lung Cell Mol Physiol

Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study

BMJ

Mechanisms of asthma and allergic inflammation
Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice