Fatty acid profi le in erythrocytes associated with serum cytokines in pediatric cystic fi brosis patients
Resumen
Objective
To analyze erythrocyte fatty acid composition and its association with serum cytokine levels in pediatric cystic fi brosis patients.
Methods
A cross-sectional study was performed at a reference center in Rio de Janeiro, Brazil. We have included all pediatric patients aged 5-19 years with confirmed cystic fibrosis diagnosis. Erythrocyte fatty acid composition and serum cytokine (TNF-α, IL-1β, IL-6 and IL-8) and C-reactive protein levels were measured. The cut-off point to determine essential fatty acids deficiency was the linoleic acid concentration of <21%.
Results
Twenty-six children (<10 years old) and thirty-one adolescents were studied. Most patients were female and heterozygous for DF508 mutation and suffered from exocrine pancreatic insufficiency. Both children and adolescents had lower linoleic acid concentration (<21%). TNF-α was the only pro-inflammatory marker whose levels were increased; the increase was greater in children. An association between fatty acid composition in erythrocytes and cytokines IL-1β and IL-6 was observed (p<0.05).
Conclusion
The pediatric cystic fibrosis patients studied presented a deficiency of essential fatty acids, and an association between fatty acid profile in erythrocytes and serum pro-inflammatory cytokines was observed. These findings highlight the importance of this type of assessment that may open new possibilities for studying pathophysiology and treating cystic fibrosis patients, such as the dietary supplementation with n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids). However, further longitudinal studies are needed for better clarification of the imbalance in lipid metabolism and inflammation in cystic fibrosis.
Citas
Courtney JM, Ennis M, Elbom JS. Cytokines and inflammatory mediators in cystic fibrosis. J Cyst Fibros. 2004;3(4):223-31. http://dx.doi.org/10.1016/j.jcf.2004.06.006
Strandvik B. Fatty acid metabolism in cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids. 2010;83(3):121-9. http://dx.doi.org/10.1016/j.plefa.2010.07.002
Calder PC, Innes JK. Omega-6 fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids. 2018;132:41-8. http://dx.doi.org/10.1016/j.plefa.2018.03.004
Roulet M, Frascarolo P, Rappaz I, Pilet M. Essential fatty acid deficiency in well-nourished young cystic fibrosis patients. Eur J Pediatr. 1997;156:952-6.
Bhura-Bandali FN, Suh M, Paul Man SF, Clandinin MT. The DF508 mutation in the cystic fibrosis transmembrane conductance regulator alters control of essential fatty acid utilization in epithelial cells biochemical and molecular action of nutrients. J Nutr. 2000;130(12):2870-5. http://dx.doi.org/10.1093/jn/130.12.2870
Seegmiller AC. Abnormal unsaturated fatty acid metabolism in cystic fibrosis: Biochemical mechanisms and clinical implications. Int J Mol Sci.2014;15(9):16083-99. http://dx.doi.org/10.3390/ijms150916083
Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, et al. Cystic Fibrosis foundation evidence-based guidelines for management of infants with Cystic Fibrosis. J Pediatr. 2009;155(6):S73-93. http://dx.doi.org/10.1016/j.jpeds.2009.09.001
Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948-68. http://dx.doi.org/10.1183/09031936.05.00035205
Zock PL, Mensink RP, Harryvan J, Vries JHM, Katan MB. Fatty acids in serum cholesteryl esters as quantitative biomarkers of dietary intake in humans. Am J Epidemiol. 1997;145(12):1114-22. 10. Maqbool A, Schall JI, Garcia-Espana F, Zemel BS, Strandvik B, Stallings VA. Serum linoleic acid status as a clinical indicator of essential fatty acid status in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2008;47(5):635-44. http://dx.doi.org/10.1097/MPG.0b013e31817fb76b
Strandvik B, Gronowitz E, Enlund F, Martinsson T, Wahlstrom J. Essential fatty acid deficiency in relation to genotype in patients with cystic fibrosis. J Pediatr. 2001;139:650-5. http://dx.doi.org/10.1067/mpd.2001.118890
Van Biervliet S, Vanbillemont G, Van Biervliet JP, Declercq D, Robberecht E, Christophe A. Relation between fatty acid composition and clinical status or genotype in cystic fibrosis patients. Ann Nutr Metab. 2007;51:541-9. http://dx.doi.org/10.1159/000114208
Van Biervliet S, Devos M, Van Biervliet JP, Robberecht E, Christophe A. Oral DHA supplementation in DF508 homozygous cystic fibrosis patients. Prostaglandins Leukot Essent Fatty Acids. 2008;78(2):109-15. http://dx.doi.org/10.1016/j.plefa.2007.12.005
Turck D, Braegger CP, Colombo C, Declercq D, Morton A, Pancheva R, et al. ESPEN-ESPGHANECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr. 2016;35(3):557. http://dx.doi.org/10.1016/j.clnu.2016.03.004
Lepage G, Levy E, Ronco N, Smith L, Galgano N, Roy CC. Direct transesterification of plasma fatty acids for the diagnosis of essential fatty acid deficiency in cystic fibrosis. J Lipid Res. 1989;30(10):1483-90.
Freedman SD, Blanco PG, Zaman MM, Shea JC, Ollero M, Hopper IK, et al. Association of cystic fibrosis with abnormalities in fatty acid metabolism. N Engl J Med. 2004;350(6):560-9. http://dx.doi.org/10.1056/NEJMoa021218
Olveira G, Olveira C, Acosta E, Espildora F, Garrido-Sanchez L, Garcia-Escobar E, et al. Fatty acid supplementation improves respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis. Arch Bronconeumol. 2010;46(2):70-7. http://dx.doi.org/10.1016/j.arbres.2009.11.001
Arab L, Akbar J. Biomarkers and the measurement of fatty acids. Public Health Nutr. 2002;5(6A):865-71. http://dx.doi.org/10.1079/PHN2002391
Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem. 2006;52(12):2265-72. http://dx.doi.org/10.1373/clinchem.2006.072322
Alicandro G, Faelli N, Gagliardini R, Santini B, Magazzu G, Biffi A, et al. A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids. 2013;88(2):163-9. http://dx.doi.org/10.1016/j.plefa.2012.10.002
Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: An 18-month controlled study. J Lipid Res. 1997;38(10):2012-22.
Zong G, Li Y, Wanders AJ, Alssema M, Zock P, Willet WC, et al. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: Two prospective longitudinal cohort studies. BMJ. 2016;355:i5796. http://dx.doi.org/10.1136/bmj.i5796
Wu MY, Li CJ, Hou MF, Chu PY. New insights into the role of inflammation in the pathogenesis of atherosclerosis. Int J Mol Sci. 2017;18(10):2034. http://dx.doi.org/10.3390/ijms18102034
Smith C, Winn A, Seddon P, Ranganathan S. A fat lot of good: Balance and trends in fat intake in children with cystic fibrosis. J Cyst Fibros. 2012;11(2):154-7. http://dx.doi.org/10.1016/j.jcf.2011.10.007
De Vizia B, Raia V, Spano C, Pavlidis C, Coruzzo A, Alessio M. Effect of an 8-month treatment with omega-3 fatty acids (eicosapentaenoic and docosahexaenoic) in patients with cystic fibrosis. J Parenter Enteral Nutr. 2003;27(1):52-7. http://dx.doi.org/10.1177/014860710302700152
Aldamiz-Echevarria L, Prieto JA, Andrade F, Elorz J, Sojo A, Lage S, et al. Persistence of essential fatty acid deficiency in cystic fibrosis despite nutritional therapy. Pediatr Res. 2009;66(2009):585-9. http://dx.doi.org/10.1203/PDR.0b013e3181b4e8d3
Hanssens L, Thiébaut I, Lefèvre N, Malfroot A, Knoop C, Duchateau J, et al. The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients: A pilot study. Prostaglandins Leukot Essent Fatty Acids. 2016;108:45-50. http://dx.doi.org/10.1016/j.plefa. 2016.03.014
Schuchardt JP, Hahn A. Bioavailability of longchain ômega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013;89(1):1-8. http://dx.doi.org/10.1016/j.plefa.2013.03.010
Goyens PLL, Spilker ME, Zock PL, Katan MB, Mensink RP. Conversion of α-linolenic acid in humans is influenced by the absolute amounts of α-linolenic acid and linoleic acid in the diet and not their ratio. Am J Clin Nutr. 2006;84(1):44-53. http://dx.doi.org/10.1093/ajcn/84.1.44
Keen C, Olin AC, Edentoft A, Gronowitz E, Strandvik B. Airway nitric oxide in patients with cystic fibrosis is associated with pancreatic function, pseudomonas infection, and polyunsaturated fatty acids. Chest. 2007;131(6):1857-64. http://dx.doi.org/10.1378/chest.06-2635
Nixon LS, Yung B, Bell SC, Elborn JS, Shale DJ. Circulating immunoreactive interleukin-6 in cystic fibrosis. Am J Respir Crit Care Med. 1998;157(6);1764-9.
Dufresne V, Knoop C, Van Muylem A, Malfroot A, Lamotte M, Opdekamp C, et al. Effect of systemic inflammation on inspiratory and limb muscle strength and bulk in cystic fibrosis. Am J Respir Crit Care Med. 2009;180(2):153-8. http://dx.doi.org/10.1164/rccm.200802-232OC
Pepys MB. C-reactive protein fifty years on. Lancet. 1981;1(8221):653-7.
Ionescu AA, Nixon LS, Evans WD, Stone MD, Lewis-Jenkins V, Chatham K, et al. Bone density, body composition, and inflammatory status in cystic fibrosis. Am J Respir Crit Care Med. 2000;162(3):789-94. http://dx.doi.org/10.1164/ajrc cm.162.3.9910118
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2023 Ana Lucia Pereira da CUNHA, Ana Carolina Carioca da COSTA, Zilton VASCONCELOS, Maria das Graças TAVARES DO CARMO, Celia Regina Moutinho de Miranda CHAVES
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.