Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD
- 230 Downloads
Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists.
Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients.
COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1β exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1β, neutrophil, and macrophage counts and smoking history. TNFα antagonists exceeded agonists in both groups and did not correlate with COPD severity.
Endogenous IL-1β antagonists appear reduced in COPD. Furthermore, IL-1β correlated with clinical aspects of disease severity, suggesting that IL-1β may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFα has limited activity in stable COPD.
KeywordsNeutrophils cytokines cytokine receptors inflammation lung
- 9.Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthews SB, Griffiths TL, Shale DL. Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;15(164):1414–8.Google Scholar
- 11.Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS, GOLD Scientific Committee. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163:1256–76.PubMedGoogle Scholar
- 16.Sankoh AJ, Hugue MF, Dubey SD. Some comments on frequently used multiple endpoint adjustment methods in clinical trials. Stat Med 1997;16:2529–42. doi:10.1002/(SICI)1097-0258(19971130)16:22<2529::AID-SIM692>3.0.CO;2-J.PubMedCrossRefGoogle Scholar
- 18.Gamble E, Qiu Y, Wang D, Zhu J, Vignola AM, Kroegel C, Morell F, Hansel TT, Pavord I, Rabe KF, Barnes NC, Jeffrey PK. Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design. Eur Respir J 2006;27:293–9. doi:10.1183/09031936.06.00027705.PubMedCrossRefGoogle Scholar
- 21.Catania A. Interactions among POMC-derived peptides and cytokines in control of the acute phase response in the aged. Italian National Research Council. http://www.aging.cnr.it/uoe/uo1_048.htm, 2007.
- 25.Rolfe MW, Standifrod TJ, Kunkel SL, Burdick MD, Gilbert AR, Lynch JP 3rd, Streiter RM. Interleukin-1 receptor antagonist expression in sarcoidosis. Am Rev Dis 1993;148:1378–84.Google Scholar
- 28.Vecil GG, Larsen PH, Corley SM, Herx LM, Besson A, Goodyer CG, Yong VW. IL-1 is a key regulator of MMP-9 expression in human neurons in culture and following mouse brain trauma in vivo. J Neurosci Res 2000;61:212–24. doi:10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9.PubMedCrossRefGoogle Scholar
- 34.Kurrie R, Lauffer L, Roder J, Kanzey EJ, Enssle KH, Seiler FR. Regulation of IL-1 activity by soluble IL-1 receptors. Behring Inst Mitt 1995;96:45–57.Google Scholar
- 37.Dubost JJ, Perrier S, Afane M, Viallard JL, Roux-Lombard P, Baudet-Pommel M, Begue C, Kemeny JL, Sauvezie B. IL-1 receptor antagonist in saliva; characterization in normal saliva and reduced concentration in Sjogren’s Syndrome. Clin Exp Immunol 1996;106:237–42. doi:10.1046/j.1365-2249.1996.d01-824.x.PubMedCrossRefGoogle Scholar
- 42.Girardin E, Roux-Lombard P, Grau GE, Suter P, Gallati H, Dayer JM. Imbalance between TNFa and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group. Immunology 1994;76:20–3.Google Scholar
- 43.Aderka D, Engelmann H, Wallach D. Soluble TNF receptors in health and disease. In: Fiers W, Buurman WA, editors. Tumor Necrosis Factor: Molecular and Cellular Biology and Clinical Relevance. Basel: Karger; 1993. p. 191–8.Google Scholar
- 44.Aderka D, Sorkine P, Abu-Abid S, Lev D, Setton A, Cope AP, Walloch D. Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion relevance to the pathophysiology of septic shock. J Clin Invest 1998;101:50–659. doi:10.1172/JCI694.CrossRefGoogle Scholar
- 45.Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;175:926–34. doi:10.1164/rccm.200607-995OC.PubMedCrossRefGoogle Scholar
- 49.Dal Negro RW, Micheletto C, Tognella S, Visconti M, Guerriero M, Sandri MF. A two stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral and non-infectious origin of COPD exacerbations. COPD 2005;2:7–16. doi:10.1081/COPD-200050680.PubMedCrossRefGoogle Scholar
- 53.Celli BR, Cote CG, Marin JM, Cassanova C, Montes de Oca M, Mendez RP, Pinto Plata V, Cabral HJ. The body mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005–12. doi:10.1056/NEJMoa021322.PubMedCrossRefGoogle Scholar
- 56.Gamble E, Grootendorst DC, Hattotuwa K, O’Shaughnessy T, Ram FS, Qiu Y, Zhu J, Vignola AM, Kroegal C, Morell F, Pavord ID, Rabe KF, Jeffery PK, Barnes NC. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers; a pooled analysis. Eur Respir J 2007;30:467–71. doi:10.1183/09031936.00013006.PubMedCrossRefGoogle Scholar