Effect of leptin on allergic airway responses in mice.
BACKGROUND
Epidemiologic data indicate that the incidence of asthma is increased in obese patients.


OBJECTIVE
Because the serum levels of the satiety hormone and proinflammatory cytokine leptin are increased in obese individuals, we sought to determine whether leptin can augment allergic airway responses.


METHODS
We sensitized and challenged BALB/cJ mice with ovalbumin. Alzet micro-osmotic pumps were implanted in the mice to deliver a continuous infusion of either saline or leptin (1.75 mug/g/d). Two days later, the mice were challenged with either aerosolized saline or ovalbumin once per day for 3 days. We measured airway responsiveness, performed bronchoalveolar lavage, and obtained blood to measure serum leptin and IgE 24 or 48 hours after the last challenge.


RESULTS
Leptin infusion increased serum leptin concentrations, which were increased further after ovalbumin sensitization and challenge. Ovalbumin challenge increased bronchoalveolar lavage fluid cells and cytokines, serum IgE, lung cytokine mRNA expression, and responses to inhaled, aerosolized methacholine. It is important to note that the changes in methacholine responsiveness and IgE were augmented in leptin- versus saline-infused mice.


CONCLUSIONS
These results indicate that serum leptin is increased during allergic reactions in the airways and may play a role in the relationship between obesity and asthma.
Shore
Stephanie A
SA
Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115-6021, USA. sshore@hsph.harvard.edu
Schwartzman
Igor N
IN
Mellema
Matthew S
MS
Flynt
Lesley
L
Imrich
Amy
A
Johnston
Richard A
RA
D000279:Administration, Cutaneous; D000485:Allergens; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D015918:Infusion Pumps, Implantable; D020738:Leptin / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D008168:Lung / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D012333:RNA, Messenger / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000209:etiology / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D020738:Leptin; D012333:RNA, Messenger; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin