모유 내 사이토카인 함량과 2 년간 추적관찰 후 알레르기 발생

Effect of cytokines in breast milk on infant during the first two-years of life

  • 김우경 (인제대학교 서울백병원 소아과) ;
  • 윤혜선 (한림대학교 강남성심병원 소아과)
  • Kim, Woo Kyung (Department of Pediatrics, Inje University College of Medicine) ;
  • Yoon, Hae-Sun (Department of Pediatrics, Hallym University Kangnam, Sacred Heart Hospital)
  • 투고 : 2007.06.22
  • 심사 : 2007.07.30
  • 발행 : 2007.09.15

초록

목 적 : 산모의 알레르기 질환 병력 유무와 초유와 모유 간에 차이가 있는지 살펴보고, 또한 이들의 모유수유 기간에 따른 자녀의 알레르기 질환 발생 유무의 차이를 보고, 생후 2세까지 발생한 알레르기 질환과 모유 내의 면역학적 인자간의 연관성을 알아보고자 하였다. 방 법 : 2002년 5월부터 2003년 2월까지 참여를 희망한 총 138명의 산모에서 알레르기 질환이 있는 산모 88명과 알레르기 질환이 없는 산모 50명으로 나누어 조사하였다. 생후 2일경 초유와 생후 4주경의 모유를 채취하여, 초유와 모유 내 IL-4, IL- 6, IL-8, IL-10, IL-13, RANTES, $TGF-{\beta}1$$TGF-{\beta}2$를 측정하였다. 이후 소아는 생후 2세까지 알레르기 질환의 발생에 대한 추적관찰을 하였으며, 초유와 모유 내의 사이토카인과의 연관성을 비교하였다. 결 과 : 알레르기 질환이 있는 산모 군에서 6개월 이상 모유 수유하는 경우가 34.4%(n=21)였고, 3개월 미만으로 수유한 경우가 55.6%(n=15)로 두군 간에 통계학적 차이는 보이지 않았다(P>0.05). 초유 내의 IL-8 농도만이(P=0.021) 알레르기 질환이 있는 산모에서 더 높게 측정되었다. 반면 초유 내의 $TGF-{\beta}1$$TGF-{\beta}2$ 농도는 알레르기 질환이 없는 산모에서 더 높게 측정되었다(P=0.013, P=0.001). 초유나 모유 내 사이토카인과 생후 2세까지 알레르기 질환이 발생한 소아 간에 통계학적인 차이를 보이지 않았다. 결 론 : 생후 2세까지 발생한 알레르기 질환과의 연관성 있는 사이토카인은 발견하지는 못했다. 알레르기 질환이 있는 산모와 알레르기 질환이 없는 산모 간에 차이를 보인 $TGF-{\beta}1$, $TGF-{\beta}2$와 IL-8이 알레르기 질환의 병인에 연관성 조사를 위해, 추후 이들에서 장기간 추적 관찰이 필요할 것으로 생각된다.

Purpose : Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. Allergic disease (AD), including atopic eczema, asthma, allergic rhinitis, and food allergy is characterized by an imbalance between cytokines produced by distinct T-helper cell subtypes. The aim of the study was to investigate the concentrations of cytokines and chemokines that were involved in allergic reactions in breast milk from allergic and nonallergic mothers and then analyse the effect of breastfeeding duration on the prevalence of allergic disease in the age of two. Methods : The breast milk samples were collected from mothers with AD (n=88) and without AD (n=47). Breast milk was collected at the second day (colostrum) and four weeks later (mature milk).The level of Interlukine (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, $TGF-{\beta}1$, $TGF-{\beta}2$, RANTES in breast milk were determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. Results : Mothers with AD had a higher concentration of IL-8 in colostrum compared with those without AD (P=0.021). But, $TGF-{\beta}1$ and $TGF-{\beta}2$ were higher concentrated in colostrum of mother without AD (P=0.013, P=0.001). Whereas concentrations of other cytokines were not significantly different between the two groups. There was no association between levels of cytokines and chemokines in the breast milk and allergic development during the first 2 years of life in the infants. Conclusion : The higher concentration of $TGF-{\beta}1$ and $TGF-{\beta}2$ in colostrum from non-allergic mothers may explain the protective effect. But, the higher concentrations of IL-8 in colostrum from allergic mothers may in part explain the controversial results on the protective effect of breastfeeding against allergic diseases. We conclude that there is no convincing evidence form a relation between cytokines in breast milk and allergic diseases in infants. Longer follow-up are necessary to evaluate the effects of breast milk components on AD.

키워드

과제정보

연구 과제 주관 기관 : 대한소아과학회

참고문헌

  1. Chandra RK. Five-year follow-up of high-risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow's milk formulas. J Pediatr Gastroenterol Nutr 1997;24:380-8 https://doi.org/10.1097/00005176-199704000-00005
  2. Oberle D, von Kries R, von Mutius E. Asthma and breast feeding. Thorax 2001;56:896 https://doi.org/10.1136/thorax.56.11.896
  3. Wright AL, Sherrill D, Holberg CJ, Halonen M, Martinez FD. Breast-feeding, maternal IgE, and total serum IgE in childhood. J Allergy Clin Immunol 1999;104:589-94 https://doi.org/10.1016/S0091-6749(99)70328-3
  4. Miyake Y, Yura A, Iki M. Breastfeeding and the prevalence of symptoms of allergic disorders in Japanese adolescents. Clin Exp Allergy 2003;33:312-16 https://doi.org/10.1046/j.1365-2222.2003.t01-1-01607.x
  5. Siltanen M, Kajosaari M, Poussa T, Saarinen KM, Savilahti E. A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age. Allergy 2003; 58:524-30 https://doi.org/10.1034/j.1398-9995.2003.00150.x
  6. Hanson LA, Korotkova M, Haversen L, Mattsby-Baltzer I, Hahn-Zoric M, Silfverdal SA, et al. Breast-feeding, a complex support system for the offspring. Pediatr Int 2002;44: 347-52 https://doi.org/10.1046/j.1442-200X.2002.01592.x
  7. Wijga AH, van Houwelingen AC, Kerkhof M, Tabak C, de Jongste JC, Gerritsen J, et al. Breast milk fatty acids and allergic disease in preschool children: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol 2006;117:440-7 https://doi.org/10.1016/j.jaci.2005.10.022
  8. Newburg DS. Innate immunity and human milk. J Nutr 2005;135:1308-12
  9. Bohme M, Svensson A, Kull I, Wahlgren CF. Hanifin's and Rajka's minor criteria for atopic dermatitis: which do 2-year-olds exhibit? J Am Acad Dermatol 2000;43:785-92 https://doi.org/10.1067/mjd.2000.110070
  10. Labbok MH. Effects of breastfeeding on the mother. Pediatr Clin North Am 2001;48:143-58 https://doi.org/10.1016/S0031-3955(05)70290-X
  11. Eregie CO. Exclusive breastfeeding and infant growth studies: reference standards for head circumference, length and mid-arm circumference/head circumference ratio for the first 6 months of life. J Trop Pediatr 2001;47:329-34 https://doi.org/10.1093/tropej/47.6.329
  12. Koppe JG. Nutrition and breast-feeding. Eur J Obstet Gynecol Reprod Biol 1995;61:73-8 https://doi.org/10.1016/0028-2243(95)02156-M
  13. Kim HS, Seo JW, Kim YJ, Lee KH, Kim JY, Ko JS, et al. A follow-up survey of mothers' antenatal breast-feeding plans. J Korean Pediatr Soc 2003;46:635-41
  14. Akbari O, Stock P, DeKruyff RH, Umetsu DT. Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 2003;15:627-33 https://doi.org/10.1016/j.coi.2003.09.012
  15. Chulada PC, Arbes SJ, Dunson D, Zeldin DC. Breast-feeding and the prevalence of asthma and wheeze in children: analyses from the Third National Health and Nutrition Examination Survey, 1988-1994. J Allergy Clin Immunol 2003;111:328-36 https://doi.org/10.1067/mai.2003.127
  16. Dell S, To T. Breastfeeding and asthma in young children: findings from a population-based study. Arch Pediatr Adolesc Med 2001;155:1261-5
  17. Benn CS, Wohlfahrt J, Aaby P, Westergaard T, Benfeldt E, Michaelsen KF, Bjorksten B,Melbye M. Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life. Am J Epidemiol 2004;160: 217-23 https://doi.org/10.1093/aje/kwh208
  18. Bergmann RL, Diepgen TL, Kuss O, Bergmann KE, Kujat J, Dudenhausen JW, Wahn U. MAS-study group. Breastfeeding duration is a risk factor for atopic eczema. Clin Exp Allergy 2002;32:205-9 https://doi.org/10.1046/j.1365-2222.2002.01274.x
  19. Kull I, Almqvist C, Lilja G, Pershagen G, Wickman M. Breast-feeding reduces the risk of asthma during the first 4 years of life. J Allergy Clin Immunol 2004;114:755-60 https://doi.org/10.1016/j.jaci.2004.07.036
  20. Friedman NJ, Zeiger RS. The role of breast-feeding in the development of allergies and asthma. J Allergy Clin Immunol 2005;115:1238-48 https://doi.org/10.1016/j.jaci.2005.01.069
  21. Fujihashi K, McGhee JR, Lue C, Beagley KW, Taga T, Hirano T, et al. Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis. J Clin Invest 1991;88:248-52 https://doi.org/10.1172/JCI115284
  22. Defrance T, Vanbervliet B, Brie`re F, Durand I, Rousset F, Banchereau J. Interleukin 10 and transforming growth factor b cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med 1992;175:671- 82 https://doi.org/10.1084/jem.175.3.671
  23. Wu CY, Brinkmann V, Cox D, Heusser C, Delespesse G. Modulation of human IgE synthesis by transforming growth factor-beta. Clin Immunol Immunopathol 1992;62:277-84 https://doi.org/10.1016/0090-1229(92)90103-U
  24. Bottcher MF, Jenmalm MC, Garofalo RP, Bjorksten B. Cytokines in breast milk from allergic and nonallergic mothers. Pediatr Res 2000;47:157-62 https://doi.org/10.1203/00006450-200001000-00026
  25. Snijders BE, Damoiseaux JG, Penders J, Kummeling I, Stelma FF, van Ree R, et al. Cytokines and soluble CD14 in breast milk in relation with atopic manifestations in mother and infant (KOALA Study). Clin Exp Allergy 2006;36:1609- 15 https://doi.org/10.1111/j.1365-2222.2006.02613.x
  26. Michie CA, Tantscher E, Schall T, Rot A. Physiological secretion of chemokines in human breast milk. Eur Cytokine Netw 1998;9:123-9
  27. Bottcher MF, Jenmalm MC, Bjorksten B, Garofalo RP. Chemoattractant factors in breast milk from allergic and nonallergic mothers. Pediatr Res 2000;47:592-7 https://doi.org/10.1203/00006450-200005000-00006
  28. Bottcher MF, Jenmalm MC, Bjorksten B. Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants. Pediatr Allergy Immunol 2003;14:35-41 https://doi.org/10.1034/j.1399-3038.2003.02120.x