Abstract
Atopic disease is characterized by an imbalance in cytokines secreted from Th1 and Th2 lymphocytes. The association between atopy and serum levels of atopy-related chemokines in umbilical cord blood (UCB) has not been evaluated. This study formulates the reference ranges of thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin (EOX), monocyte chemotactic protein 1 (MCP-1), and interferon-γ-inducible protein 10 (IP-10) in UCB of term neonates and investigates the relation between these chemokines and the development of atopy during infancy. The concentrations of total IgE and chemokines in UCB serum were measured by microparticle immunoassay and sandwich enzyme immunoassay, respectively. A total of 124 singleton healthy newborns were investigated. Fifty-three (43%) infants had family history of allergic diseases, and 26 (21%) had increased serum total IgE concentrations. The median (interquartile range) serum TARC, MDC, EOX, MCP-1, and IP-10 concentrations, in pg/mL, were 425 (300–639), 786 (561–1050), 36 (28–45), 156 (116–205), and 38 (29–49), respectively. Multiparity was associated with increased serum MDC (p = 0.017). Serum chemokine concentrations were not associated with total IgE levels or family history of allergies. The median (interquartile range) serum MDC concentrations in newborns who developed wheezing during infancy and those without wheezing were 1259 pg/mL (945–1523) and 782 pg/mL (551–992), respectively (p = 0.010). This study provides reference ranges of Th-specific chemokines in UCB serum of singleton term neonates. Increased serum MDC concentrations at birth are associated with the occurrence of wheezing during infancy.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BRD:
-
bronchopulmonary dysplasia
- EOX:
-
eotaxin
- IFN-γ:
-
interferon-γ
- IP-10:
-
interferon-γ-inducible protein 10
- IQR:
-
interquartile range
- MCP-1:
-
monocyte chemotactic protein 1
- MDC:
-
macrophage-derived chemokine
- TARC:
-
thymus and activation-regulated chemokine
- UCB:
-
umbilical cord blood
References
Romagnani S 2000 The role of lymphocytes in allergic disease. J Allergy Clin Immunol 105: 399–408
Baggiolini M, Dewald B, Moser B 1997 Human chemokines: an update. Ann Rev Immunol 15: 675–705
Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F 1998 Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187: 129–134
Sallusto F, Lenig D, Mackay CR, Lanzavecchia A 1998 Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 187: 875–883
Mochizuki M, Bartels J, Mallet AI, Christophers E, Schroder JM 1998 IL-4 induces eotaxin: a possible mechanism of selective eosinophil recruitment in helminthic infection and atopy. J Immunol 160: 60–68
Miotto D, Christodoulopoulos P, Olivenstein R, Taha R, Cameron L, Tsicopoulos A, Tonnel AB, Fahy O, Lafitte JJ, Luster AD, Wallaert B, Mapp CE, Hamid Q 2001 Expression of IFN-γ-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in TH1- and TH2-mediated lung diseases. J Allergy Clin Immunol 107: 664–670
Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O 1997 The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem 272: 15036–15042
Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C, Buonsanti C, Miotto D, Mapp C, Villa A, Arrigoni G, Fabbri LM, Sinigaglia F 2001 The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 107: 1357–1364
Andrew DP, Chang MS, McNinch J, Wathen ST, Rihanek M, Tseng J, Spellberg JP, Elias CG 1998 STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol 161: 5027–5038
Bonecchi R, Sozzani S, Stine JT, Luini W, D'Amico G, Allavena P, Chantry D, Mantovani A 1998 Divergent effects of interleukin-4 and interferon-gamma on macrophage-derived chemokine production: an amplification circuit of polarized T helper 2 responses. Blood 92: 2668–2671
Car BD, Meloni F, Luisetti F, Semenzato F, Gialdroni-Grassi G, Walz A 1994 Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med 149: 655–659
Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL 1996 Role of monocyte chemotactic protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol 157: 4602–4608
Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, Yoshie O 1999 Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11: 81–88
Taub DD, Lloyd AR, Conlon K, Wang JM, Ortaldo JR, Harada A, Matsushima K, Kelvin DJ, Oppenheim JJ 1993 Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 177: 1809–1814
Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD 2000 A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 162: 1403–1406
Husby S, Holm NV, Christensen K, Skoy R, Morling N, Petersen PH 1996 Cord blood immunoglobulin E in like-sexed monozygotic and dizygotic twins. Clin Genet 50: 332–338
Kaan A, Dimich-Ward H, Manfreda J, Becker A, Watson W, Ferguson A, Chan H, Chan-Yeung M 2000 Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months. Ann Allergy Asthma Immunol 84: 37–42
Sullivan SE, Staba SL, Gersting JA, Hutson AD, Theriaque D, Christensen RD, Calhoun DA 2002 Circulating concentrations of chemokines in cord blood, neonates, and adults. Pediatr Res 51: 653–657
Mellembakken JR, Aukrust P, Hestdal K, Ueland T, Åbyholm T, Videm V 2001 Chemokines and leukocytes activation in the fetal circulation during preeclampsia. Hypertension 38: 394–398
Fillion I, Ouellet N, Simard M, Bergeron Y, Sato S, Bergeron MG 2001 Role of chemokines and formyl peptides in pneumococcal pneumonia-induced monocyte-macrophage recruitment. J Immunol 166: 7353–7361
Zhang Y, Luxon BA, Casola A, Garofalo RP, Jamaluddin M, Brasier AR 2001 Expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cDNA microarrays. J Virol 75: 9044–9058
Matsukawa A, Hogaboam CM, Lukacs NW, Lincoln PM, Evanoff HL, Kunkel SL 2000 Pivotal role of the CC chemokine, macrophage-derived chemokine, in the innate immune response. J Immunol 164: 5362–5368
Terada N, Nomura T, Kim WJ, Otsuka Y, Takahashi R, Kishi H, Yamashita T, Sugawara N, Fukuda S, Ikeda-Ito T, Konno A 2001 Expression of C-C chemokine TARC in human nasal mucosa and its regulation by cytokines. Clin Exp Allergy 31: 1923–1931
Vestergaard C, Bang K, Gesser B, Yoneyama H, Matsushima K, Larsen CG 2000 A Th2 chemokine, TARC, produced by keratinocytes may recruit CLA+CCR4+ lymphocytes into lesional atopic dermatitis skin. J Invest Dermatol 115: 640–646
Kakinuma T, Nakamura K, Wakugawa M, Mitsui H, Tada Y, Saeki H, Torii H, Asahina A, Onai N, Matsushima K, Tamaki K 2001 Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol 107: 535–541
Leung TF, Wong CK, Chan IHS, Ip WK, Lam CWK, Wong GWK 2002 Plasma concentration of thymus and activation-regulated chemokine is elevated in childhood asthma. J Allergy Clin Immunol 110: 404–409
Leung TF, Ma KC, Hon KL, Lam CWK, Wan H, Li CY, Chan IHS 2003 Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children. Pediatr Allergy Immunol 14: 296–301
D'Angio CT, Johnston CJ, Wright TW, Reed CK, Finkelstein JN 1998 Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia. Exp Lung Res 24: 685–702
Johnston CJ, Oberdorster G, Gelein R, Finkelstein JN 2000 Newborn mice differ from adult mice in chemokine and cytokine expression to ozone, but not to endotoxin. Inhal Toxicol 12: 205–224
Yamamoto C, Kojima T, Hattori K, Nogi S, Imamura H, Tsubura A, Kobayashi Y 1996 Eosinophilia in premature infants: correlation with chronic lung diseases. Acta Paediatr 85: 1232–1235
Raghavender B, Smith JB 1997 Eosinophil cationic protein in tracheal aspirates of preterm infants with bronchopulmonary dysplasia. J Pediatr 130: 944–947
Evans M, Palta M, Sadek M, Weinstein MR, Peters ME 1998 Associations between family history of asthma, bronchopulmonary dysplasia, and childhood asthma in very low birth weight children. Am J Epidemiol 148: 460–466
Elder DE, Hagan R, Evans SF, Benninger HR, French NP 1996 Recurrent wheezing in very preterm infants. Arch Dis Child Fetal Neonatal Ed 74: F165–F171
Acknowledgements
We thank midwives who work in the obstetric unit for help with UCB collection.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by a Direct Grant for Research from The Chinese University of Hong Kong.
APPENDIX 1
APPENDIX 1
DETAILS OF THE QUESTIONNAIRE USED FOR TELEPHONE INTERVIEW
-
1
Has your child ever had attacks of wheezing? (Wheeze ever)
-
2
Does your child usually have a cough apart from colds? (Cough apart from cold)
-
3
Has any doctor told you that your child has asthma or bronchitis? (MD asthma)
-
4
Does your child have nasal discharge or sneezing apart from cold since birth? (Nasal symptoms apart from cold)
-
5
Has any doctor told you that your child has allergic rhinitis? (MD allergic rhinitis)
-
6
Has your child ever had persistent (>4 wk) itchy flexural rash? (Itchy flexural rash)
-
7
Has any doctor told you that your child has atopic dermatitis? (MD atopic dermatitis)
Rights and permissions
About this article
Cite this article
Leung, TF., Ng, PC., Tam, WH. et al. Helper T-Lymphocyte–Related Chemokines in Healthy Newborns. Pediatr Res 55, 334–338 (2004). https://doi.org/10.1203/01.PDR.0000102456.03407.84
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000102456.03407.84


