High serum levels of tumour necrosis factor-alpha and interleukin-8 in severe asthma: markers of systemic inflammation?

Clin Exp Allergy. 2006 Nov;36(11):1373-81. doi: 10.1111/j.1365-2222.2006.02502.x.


Background: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma.

Objective: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels.

Methods: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2].

Results: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics.

Conclusion: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Asthma / diagnosis
  • Asthma / immunology*
  • Biomarkers / blood
  • Breath Tests
  • Case-Control Studies
  • Eosinophils / pathology
  • Female
  • Humans
  • Interleukin-13 / blood
  • Interleukin-16 / blood
  • Interleukin-8 / blood*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutrophils / pathology
  • Nitric Oxide / analysis
  • Respiratory Function Tests
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / blood*


  • Biomarkers
  • Interleukin-13
  • Interleukin-16
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide