Skip to main content
Log in

Elevated TNFα production in whole blood in patients with severe COPD: the potential link to disease severity

Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

OBJECTIVE: The relationship between tumour necrosis factor-α (TNFα), severity of pulmonary disease and nutritional depletion in chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to clarify the role of lipopolysaccharide (LPS) as a potential stimulus of cytokine production and the role of these cytokines in the alteration of body composition in patients with different degrees of COPD. PATIENTS AND METHODS: We studied 29 weight-stable out-patients with different severites of COPD who had no evidence of recent infection or significant co-morbidity. Baseline serum TNFα levels and TNFα response to LPS in whole blood were measured in patients and 20 aged matched controls. RESULTS: Serum TNFα was significantly elevated in patients versus controls (2.1 ± 0.3 vs. 1.1 ± 0.1 pg/ml, mean ± SEM, P = 0.007). In patients with COPD, we found a significant correlation between serum TNFα levels and disease severity, assessed as FEV1 %predicted (r = 0.49, P = 0.02). Response to lipopolysaccharide did not differ significantly between patients and controls. However, within the patient group those with more severe disease (FEV1 ≤ 30% predicted, n = 12) had an enhanced response compared to patients with mild-to-moderate disease (all P < 0.05 for LPS > 1 ng/ml). Spontaneous TNFα production was 5.0 times higher in patients with severe COPD compared to mild-to-moderate COPD (P = 0.02). There was no relation between body composition and serum TNFα or TNFα response to LPS. CONCLUSION: Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFα response in COPD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J (2007) Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176: 532–555

    Article  PubMed  Google Scholar 

  • Joppa P, Petrásová D, Stancák B, Dorková Z, Tkácová R (2007) Oxidative stress in patients with COPD and pulmonary hypertension. Wien Klin Wochenschr 119: 428–434

    Article  PubMed  CAS  Google Scholar 

  • Barnes PJ (2008) The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118: 3546–3556

    Article  PubMed  CAS  Google Scholar 

  • Firlei N, Lamprecht B, Schirnhofer L, Kaiser B, Studnicka M (2007) The prevalence of COPD in Austria –the expected change over the next decade. Wien Klin Wochenschr 119: 513–518

    Article  PubMed  Google Scholar 

  • De Boer WI (2002) Cytokines and therapy in COPD: a promising combination? Chest 121: 209S–218S

    Article  PubMed  CAS  Google Scholar 

  • Schols AM, Buurman WA, Staal van den Brekel AJ, Dentener MA, Wouters EF (1996) Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 51: 819–824

    Article  PubMed  CAS  Google Scholar 

  • von Haehling S, Lainscak M, Springer J, Anker SD (2009) Cardiac cachexia: a systematic overview. Pharmacol Ther, doi: 10.1016/j.pharmthera.2008.09.009

  • von Haehling S, Genth-Zotz S, Anker SD, Volk HD (2002) Cachexia: a therapeutic approach beyond cytokine antagonism. Int J Cardiol 85: 173–183

    Article  PubMed  CAS  Google Scholar 

  • Wagner PD (2008) Possible mechanisms underlying the development of cachexia in COPD. Eur Respir J 31: 492–501

    Article  PubMed  CAS  Google Scholar 

  • Lainscak M, Podbregar M, Anker SD (2007) How does cachexia influence survival in cancer, heart failure and other chronic diseases? Curr Opin Support Palliat Care 1: 299–305

    Article  PubMed  Google Scholar 

  • Keatings VM, Collins PD, Scott DM, Barnes PJ (1996) Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 153: 530–534

    PubMed  CAS  Google Scholar 

  • Bresser P, Out TA, van Alphen L, Jansen HM, Lutter R (2000) Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 162: 947–592

    PubMed  CAS  Google Scholar 

  • Aaron SD, Angel JB, Lunau M, Wright K, Fex C, Le Saux N, Dales RE (2001) Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 163: 349–355

    PubMed  CAS  Google Scholar 

  • Di Francia M, Barbier D, Mege JL, Orehek J (1994) Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 150: 1453–1455

    PubMed  CAS  Google Scholar 

  • Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthews SB, Griffiths TL, Shale DJ (2001) Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164: 1414–1418

    PubMed  CAS  Google Scholar 

  • de Godoy I, Donahoe M, Calhoun WJ, Mancino J, Rogers RM (1996) Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients. Am J Respir Crit Care Med 153: 633–637

    PubMed  CAS  Google Scholar 

  • Nguyen LT, Bedu M, Caillaud D, Beaufrere B, Beaujon G, Vasson M, Coudert J, Ritz P (1999) Increased resting energy expenditure is related to plasma TNF-alpha concentration in stable COPD patients. Clin Nutr 18: 269–274

    Article  PubMed  CAS  Google Scholar 

  • Schols AM, Creutzberg EC, Buurman WA, Campfield LA, Saris WH, Wouters EF (1999) Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 160: 1220–1226

    PubMed  CAS  Google Scholar 

  • Vandenbergh E, Van de Woestijne KP, Gyselen A (1967) Weight changes in the terminal stages of chronic obstructive pulmonary disease. Relation to respiratory function and prognosis. Am Rev Respir Dis 95: 556–566

    PubMed  CAS  Google Scholar 

  • Decramer M, Gosselink R, Troosters T, Verscheueren M, Evers G (1997) Muscle weakness is related to utilization of health care resources in COPD patients. Eur Resp J 10: 417–423

    Article  CAS  Google Scholar 

  • Steiner MC, Barton RL, Singh SJ, Morgan MD (2002) Bedside methods versus dual energy X-ray absorptiometry for body composition measurement in COPD. Eur Respir J 19: 626–631

    Article  PubMed  CAS  Google Scholar 

  • Lerario MC, Sachs A, Lazaretti-Castro M, Saraiva LG, Jardim JR (2006) Body composition in patients with chronic obstructive pulmonary disease: which method to use in clinical practice? Br J Nutr 96: 86–92

    Article  PubMed  CAS  Google Scholar 

  • Takabatake N, Nakamura H, Abe S, Inoue S, Hino T, Saito H, Yuki H, Kato S, Tomoike H (2000) The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161: 1179–1184

    PubMed  CAS  Google Scholar 

  • Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, Maltais F (1998) Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158: 629–634

    PubMed  CAS  Google Scholar 

  • Gea JG, Pasto M, Carmona MA, Orozco-Levi M, Palomeque J, Broquetas J (2001) Metabolic characteristics of the deltoid muscle in patients with chronic obstructive pulmonary disease. Eur Respir J 17: 939–945

    Article  PubMed  CAS  Google Scholar 

  • Polkey MI, Kyroussis D, Hamnegard C-H, Mills GH, Green M, Moxham J (1996) Diaphragm strength in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 154: 1310–1317

    PubMed  CAS  Google Scholar 

  • von Haehling S, Anker SD (2005) Future prospects of anticytokine therapy in chronic heart failure. Expert Opin Investig Drugs 14: 163–176

    Article  PubMed  CAS  Google Scholar 

  • Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, Poole-Wilson PA, Coats AJ, Anker SD (1999) Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 353: 1838–1842

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sabine Genth-Zotz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Haehling, S., Hopkinson, N., Polkey, M. et al. Elevated TNFα production in whole blood in patients with severe COPD: the potential link to disease severity. Wien Klin Wochenschr 121, 303–308 (2009). https://doi.org/10.1007/s00508-009-1186-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-009-1186-7

Keywords

Navigation