TABLE 2

Murine models involving a combination of exposures to allergens and cigarette smoke (CS)

StrainExperimental methodKey features of modelFirst author [ref.]
BALB/c WT3 weeks of CS (5 days·week−1, 5 cigarettes for 7 min, 4 times·day−1) concurrent with OVA challenge via aerosol for 7 min, 4 times·day−1
  • ↑ serum IgE and IgG1

  • ↑ eosinophils, lymphocytes and dendritic cells in BALF

  • ↑ dendritic cells, goblet cell hyperplasia, CD4+ and CD8+ T-cells in lung tissue

  • ↑ CCL17 and IFN-γ in BALF

  • ↑ IL-5 in lymph node cell cultures

Moerloose [167]
BALB/c WT3 weeks of HDM intranasally (5 days·week−1) followed by 2 weeks of concurrent HDM+CS (5 days·week−1, 12 cigarettes for 50 min, 1 or 2 times·day−1)
  • ↓ total cell count, mononuclear cells, neutrophils in BALF

  • ↓ eosinophils in BALF and lung tissue

  • ↓ B-cells and serum IgE

  • ↓ VCAM-1 and eotaxin-1

  • No significant differences in airway resistance

Botelho [168]
C57BL/6 WT and CD44 deficient3 weeks of CS (5 days·week−1, 5 cigarettes 3 times·day−1) with HDM intranasally once per week at the end of CS exposure
  • No significant differences in AHR

  • ↑ CD4+ and CD8+ T-cells, and hyaluronic acid in BALF

  • ↑ goblet cell metaplasia

  • ↑ IL-4, IL-5, IL-13 in lymph node cell culture

  • CD44 deletion resulted in:

    • o ↓ number of eosinophils, dendritic cells, neutrophils, CD4+ and CD8+ T-cells in BALF

    • o ↓ IL-4, IL-5 and IL-13 in lymph node cell culture

    • o ↓ goblet cell metaplasia

Kumar [169]
BALB/c WTTriple OVA, cockroach antigen, and HDM intraperitoneally on days 0, 14, and 21 followed by 6 weeks of allergen challenge concurrent with CS (5 days·week−1, 4 cigarettes·day−1)
  • ↑ total cell count, eosinophils, macrophages, neutrophils, lymphocytes, IL-4 and IL-5; however, all except neutrophils were higher with allergen alone

  • ↑ IL-10, IL-12, IL-1β, and CXCL1 in BALF

  • ↓ compliance versus control following methacholine challenge, no increase in resistance observed

Tilp [170]
C57BL/6J WTLPS intranasally at days 0 and 14 followed by 10 weeks of CS (6 days·week−1, 9 cigarettes for 2 h, 2 times·day−1)
  • Impaired lung function

  • ↑ total cells counts in BALF (↑ neutrophils, lymphocytes and macrophages)

  • ↑ IL-6 and CXCL1 in BALF

  • Goblet cell hyperplasia

  • Bronchial wall thickening

Shu [171]
BALB/c WTOVA intraperitoneally on days 0 and 14. OVA aerosol administered daily from days 24 to 41 in conjunction to CS (15 cigarettes for 40 min, 2 times·day−1)
  • ↑ total cell count and ↑% of neutrophils in BALF

  • ↑ AHR

  • ↑ serum TNF-α and CXCL1

  • ↓ HDAC2 but ↑ phosphorylated Akt in lung sections measured using integrated optical density

Xia [172]

WT: wild-type; OVA: ovalbumin; Ig: immunoglobulin; BALF: bronchoalveolar lavage fluid; IFN: interferon; IL: interleukin; HDM: house dust mite; VCAM-1: vascular cell adhesion molecule-1; TNF: tumour necrosis factor; CXCL1: C-X-C motif chemokine ligand 1; LPS: lipopolysaccharide; AHR: airway hyperresponsiveness; HDAC2: histone deacetylase 2; Akt: protein-kinase B.