Nevin İLHAN, Ilgın KARACA, Teyfik TURGUT, Mehmet Hamdi MUZ, Yasemin DEVECİ, Figen DEVECİ

Kronik obstrüktif akciğer hastalığı olan olgularda serum grelin, IL-6 ve TNF-α düzeyleri

Kronik obstrüktif akciğer hastalığı (KOAH)nda gelişen kaşekside endokrin faktörlerin de rol oynayabildiği belirtilmektedir. Grelinin kaşektik KOAHlı olgularda arttığı bildirilmiş fakat aradaki ilişki istatistiksel olarak güçlendirilmemiştir. Çalış- mamızda KOAHda serum grelin düzeylerinin belirlenmesi, proinflamatuvar sitokinlerle ilişkisinin değerlendirilmesi ve ka- şeksi ile birlikteliğinin olup olmadığının araştırılması amaçlanmıştır. Çalışmamıza 60 stabil KOAHlı hasta ve 15 sağlıklı gö- nüllü alındı. KOAHlı hastalar beden kitle indekslerine göre kaşektik ve normal kilolu olmak üzere iki gruba ayrıldı. Tüm olgularda spirometrik inceleme yapılarak serum tümör nekroz faktörü-alfa (TNF-α), interlökin-6 (IL-6) ile grelin düzeyleri öl- çüldü. KOAHlı hastalar kontrol grubu ile karşılaştırıldığında serum grelin düzeyleri istatistiksel olarak anlamlı düşük, TNF-α ve IL-6 düzeyleri istatistiksel olarak anlamlı yüksekti. Kaşektik KOAHlı hastalarda serum grelin düzeyi normal kilolu KOAHlı hastalara göre istatistiksel olarak anlamlı düşük, IL-6 düzeyi ise anlamlı yüksekti. Serum TNF-α düzeyi de ka- şektik KOAHlı hastalarda daha yüksek bulunmakla birlikte bu yükseklik anlamlı düzeyde değildi. KOAHlı hastalarda serum grelin düzeyleri beden kitle indeksi arasında pozitif korelasyon saptandı. Sonuç olarak; KOAHda gelişen kilo kaybında artmış proinflamatuvar sitokinlerin yanında azalmış serum aktif grelin düzeylerinin katkısının olabileceği düşünülmüştür

Serum ghrelin, IL-6 and TNF-α levels in patients with chronic obstructive pulmonary disease

It is determined that endocrine factors can play role on cachexia in chronic obstructive pulmonary disease (COPD). High levels of ghrelin is reported in cachectic COPD cases but its relation couldn t shown statistically. In our study, it is aimed to detect serum ghrelin levels in COPD, its relation with proinflammatory cytokines and whether serum ghrelin is associated with cachexia. Sixty stable COPD patients and 15 healthy volunteers were included in the study. COPD patients were divided into two groups, cachectic and normal weight, according to their body mass index. Spirometric assessments were performed and serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and ghrelin levels were measured in all cases. When COPD patients were compared with control group; serum ghrelin levels were statistically lower, TNF-α and IL- 6 levels were statistically higher in COPD group. For cachectic COPD patients; serum ghrelin levels were statistically lower and IL-6 levels were statistically higher, compared with normal weight COPD patients. Although, serum TNF-α levels were higher for cachectic COPD patients; these levels were not significant. Positive correlation between serum ghrelin levels and body mass index was detected in patients with COPD. As a result; it is thought that increased proinflammatory cytokins and decreased serum active ghrelin levels may contribute to the development of weight loss.

PDF

___

1. Celi BR, MacNee W, Agusti A, et al. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004; 23: 932-46.
2. Mostert R, Goris A, Weling-Scheepers C, et al. Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease. Respir Med 2000; 94: 859-67.
3. Godoy I, Donahoe M, Calhoun WJ, et al. Elevated TNFalpha production by peripheral blood monocytes of weight-losing COPD patients. Am J Respir Crit Care Med 1996; 153: 633-7.
4. Van Helvoort HA, Heijdra YF, Thijs HM, et al. Exercise-induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc 2006; 38: 1543-52.
5. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growthhormone-releasing acytlated peptide from stomach. Nature 1999; 402: 656-60.
6. Marzullo P, Verti B, Savia G, et al. The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure. J Clin Endocrinol Metab 2004; 89: 936-9.
7. Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 2003; 9: 774-8.
8. Nagaya N, Uematsu M, Kojima M, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001; 104: 2034-8.
9. Itoh T, Nagaya N, Yoshikawa M, et al. Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Res Crit Care Med 2004; 170: 879-82.
10. Luo FM, Liu XJ, Li SQ, et al. Circulating ghrelin in patients with chronic obstructive pulmonary disease. Nutrition 2005; 21: 793-8.
11. Veldee MS. Nutrition. In: Burtis CA, Ashwood ER (eds). Tietz Textbook of Clinical Chemistry. 2nd ed. Philadelphia: WB Saunders Company, 1994: 1236-74.
12. Standardized lung function testing. Official statement of the European Respiratory Society. Eur Respir J 1993; 6: 16.
13. Joppa P, Petrasova D, Stancak B, Tkacova R. Systemic inflammation in patients with COPD and pulmonary hypertension. Chest 2006; 130: 326-33.
14. Sahebjami H, Sathianpitayakul E. Influence of body weight on the severity of dyspnea in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 886-90.
15. Stankiwicz W, Dabrowski MP, Chcialowski A, Plusa T. Cellular and cytokine immunregulation in patients with COPD and bronchial asthma. Mediators Inflammation 2002; 11: 307-12.
16. Wang S, Xu F, Chen Y. Detection and signifiance of IL-8, 6, TNF-alpha in sputa from patients with COPD. Zhonghua Jie He He Hu Xi Za Zhi 2000; 23: 465-7.
17. Deveci F, İlhan N, Erdem EŞ, Muz MH. Plasma leptin concentrations in patients with stable chronic obstructive pulmonary disease. Turkish Respiratory Journal 2005; 6: 139-44.
18. Vernooy JH, Kucukaycan M, Jacobs JA, et al. Local and systemic inflammation in patients with COPD: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002; 166: 1218-24.
19. Song W, Zhao J, Li Z. IL-6 in bronchoalveolar lavage fluid from patients with COPD. Chin Med J (Eng) 2001; 114: 1140-2.
20. Bucchioni E, Kharitonov SA, Allegra L, Barnes PJ. High levels of IL-6 in the exhaled breath condensate of patients with COPD. Respir Med 2003; 97: 1299-302.
21. Dantzer R. Cytokine induced sickness behaviour: mechanisms and implications. Ann N Y Acad Sci 2001; 933: 222-34.
22. Hart BL. Biological basis of the behaviour of sick animals. Neurosci Biobehav Rev 1988; 12: 123-37. 23. Kotler DP. Cachexia. Ann Intern Med 2000; 133: 622-34.
24. Wagner PD. Possible mechanisms underly the development of cachexia in COPD. Eur Respir J 2008; 31: 492-501.
25. Karadağ F, Kirdar S, Karul A, Ceylan E. The value of Creactive protein as a marker of systemic inflamamation in stable chronic obtructive pulmonary disease. Eur J Intern Med 2008; 19: 104-8.
26. Dı Francia M, Barbier D, Mege JL, Orehek J. Tumor necrosis factor-levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994; 150: 1453-5.
27. Eid AA, lonescu AA, Nixon LS, et al. Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 1414-8.
28. Takabatake N, Nakamura H, Minanilhaba O, et al. A novel pathophysiologic phenomenin cachexic patients with chronic obstructive pulmonary disease: the relationship between the circadion rhythm of circulating leptin and the very low-freqency component of heart rate variability. Am J Respir Crit Care Med 2001; 163: 1314-9.
29. Yang Yi-Meng, Sun Tie-Ying, Liu Xin-Min. The role of serum leptin and tumor nekrosis factor-alpha malnutrition of male chronic obstructive pulmonary disease patients. Chin Med J 2006; 119: 628-33.
30. Broekhuizen R, Grimble RF, Howell WM, et al. Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1-511 single nükleotide polymorphism. Am J Clin Nutr 2005; 82: 1059-64.
31. Van der Vaart H, Koeter GH, Postma DS, et al. First study of inxlimab treatment in patients with choronic pulmonary disease. Am J Respir Crit Care Med 2005; 172: 465-9.
32. Başyiğit İ, Yıldız F, Yıldırım E, et al. Astımlı ve KOAHlı hastalarda vücut kitle indeksi ile balgam ve serum TNF- α düzeyi arasındaki ilişki. Tuberk Toraks 2004; 52: 256- 61.
33. Solary E, Dubrez L, Eymin B. The role of apopitosis in the pathogenesis and treatment of diseases. Eur Respir J 1996; 9: 1293-305.
34. Yıng BW, Song XB, Fan H, et al. Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic obstructive pulmonary disease. J Int Med Res 2008; 36: 1371-7.
35. Otero M, Noguerias R, Lago F, et al. Chronic inflammation modulates ghrelin levels in humans and rat. Rheumatology (Oxford) 2004; 89: 2136-41.
36. Harsch IA, Konturek PC, Koebnıck C, et al. Leptin and ghrelin levels in patients with obstructive sleep apnea: effect of CPAP treatment. Eur Respir J 2003; 22: 251-7.
37. Nagaya N, Itoh T, Murakami S, et al. Treatment of cachexia with ghrelin in patients with COPD. Chest 2005; 128: 1187-91.