Dietary zinc mediates inflammation and protects against wasting and metabolic derangement caused by sustained cigarette smoke exposure in mice.
In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that appetite loss, muscle wasting and poor nutrition are features of chronic obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself accompanied by growth retardation and appetite loss, we hypothesised that dietary Zn limitation would not only worsen airway inflammation but also exaggerate metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn supplementation would lessen inflammation. Mice were exposed to CS [2× 2RF, 3×/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn was measured by fluorometric assay. Inflammatory, metabolic and Zn transport markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma labile zinc (0-0.18 μM) than mice fed moderate (0.61-0.98 μM) or high (0.77-1.1 μM) Zn diets (SDs 0.1-0.4, n = 8-10). Smoke exposure increased plasma and BAL labile Zn (1.5-2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P < 0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus and tibialis anterior muscle mass were affected by both smoke and dietary Zn in the order of 3-7%. The 50-60% reduction in alveolar macrophages in Zn-supplemented mice supports our evolving hypothesis that Zn is an important anti-inflammatory mediator of airway inflammation. Restoring airway Zn levels through dietary supplementation may lessen the severity of lung inflammation when Zn intake is low.
Lang
Carol J
CJ
Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia. carol.lang@adelaide.edu.au
Hansen
Michelle
M
Roscioli
Eugene
E
Jones
Jessica
J
Murgia
Chiara
C
Leigh Ackland
Margaret
M
Zalewski
Peter
P
Anderson
Gary
G
Ruffin
Richard
R
D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D012907:Smoking / Q000009:adverse effects*; D019282:Wasting Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D015032:Zinc / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*
D015032:Zinc