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Vol. 94, No. 1, 2008
Issue release date: June 2008
Neonatology 2008;94:8–15

Cytokine Expression in Response to Bacterial Antigens in Preterm and Term Infant Cord Blood Monocytes

Tatad A.M.F. · Nesin M. · Peoples J. · Cheung S. · Lin H. · Sison C. · Perlman J. · Cunningham-Rundles S.
aDepartment of Pediatrics, Host Defenses Program, bDivision of Hematology/Oncology, cDivision of Neonatology, dWeill Cornell Medical College, and eBiostatistics Unit, North Shore-LIJ Research Institute, Manhasset, N.Y., USA

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Background: Neonatal susceptibility to bacterial infection is associated with an immature immune system, but the role of different bacterial antigens in specific responses is largely unknown. Objective: To evaluate differences in intracellular cytokine response to physiologically relevant bacterial antigens in term and preterm infants as compared with adults. Methods: Cord blood samples from preterm and term neonates and adult peripheral blood samples were cultured ex vivo with and without whole heat-killed bacteria. Intracellular leukocyte production of interleukin (IL)-6, IL-10, IL-12, and IL-8 responses was assessed by flow cytometry. Results: Monocytes were the primary producers of all mediators. Escherichia coli was the most potent stimulant. Lactobacillus plantarum299v activated fewer monocytes as compared with E. coli for all responses (p < 0.05), except for IL-12 in term neonates. IL-6 response to Staphylococcus epidermidis was lower in both groups of neonates as compared with adults (p = 0.023 and p = 0.001). IL-8 response to S. epidermidis was lower in term as compared with preterm neonates and adults (p = 0.003). IL-10 response to group B streptococci was lower in term neonates as compared with adults and higher in preterm as compared with term neonates (p = 0.015). Conclusions: Monocytes from term neonates compared to preterm neonates show a downregulated anti-inflammatory response to specific bacteria. High neonatal response to pathogenic E. coli in the preterm infant could cause uncontrolled inflammatory response, while lower IL-6 response to S. epidermidis in neonates may indicate a basis for vulnerability to S. epidermidis infection.

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  1. Wilson CB: Immunologic basis for increased susceptibility of the neonate to infection. J Pediatr 1986;108:1–12.
  2. Nesin M, Cunningham-Rundles S: Cytokines and neonates. Am J Perinatol 2000;17:393–404.
  3. Protonotariou E, Malamitsi-Puchner A, Rizos D, Papagianni B, Moira E, Sarandakou A, Botsis D: Age-related differentiations of Th1/Th2 cytokines in newborn infants. Mediators Inflamm 2004;13:89–92.
  4. Kotiranta-Ainamo A, Rautonen J, Rautonen N: Imbalanced cytokine secretion in newborns. Biol Neonate 2004;85:55–60.
  5. Delespesse G, Yang LP, Ohshima Y, Demeure C, Shu U, Byun DG, Sarfati M: Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors. Vaccine 1998;16:1415–1419.
  6. Malhotra I, Mungai P, Muchiri E, Ouma J, Sharma S, Kazura JW, King CL: Distinct Th1- and Th2-type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. Infect Immun 2005;73:3462–3470.
  7. Karlsson H, Hessle C, Rudin A: Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora. Infect Immun 2002;70:6688–6696.
  8. Bos NA, Jiang HQ, Cebra JJ: T cell control of the gut IgA response against commensal bacteria. Gut 2001;48:762–764.
  9. Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL: Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 2004;172:1118–1124.
  10. Gasparoni A, Ciardelli L, Avanzini A, Castellazzi AM, Carini R, Rondini G, Chirico G: Age-related changes in intracellular TH1/TH2 cytokine production, immunoproliferative T lymphocyte response and natural killer cell activity in newborns, children and adults. Biol Neonate 2003;84:297–303.
  11. Marodi L: Deficient interferon-gamma receptor-mediated signaling in neonatal macrophages. Acta Paediatr Suppl 2002;91:117–119.
  12. Marodi L, Goda K, Palicz A, Szabo G: Cytokine receptor signalling in neonatal macrophages: defective STAT-1 phosphorylation in response to stimulation with IFN-gamma. Clin Exp Immunol 2001;126:456–460.
  13. Jiang Q, Azuma E, Hirayama M, Iwamoto S, Kumamoto T, Kobayashi M, Yamamoto H, Sakurai M, Komada Y: Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factor. Pediatr Int 2001;43:334–339.
  14. Schultz C, Temming P, Bucsky P, Gopel W, Strunk T, Hartel C: Immature anti-inflammatory response in neonates. Clin Exp Immunol 2004;135:130–136.
  15. Berner R, Welter P, Brandis M: Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae. Pediatr Res 2002;51:304–309.
  16. Goepfert AR, Andrews WW, Carlo W, Ramsey PS, Cliver SP, Goldenberg RL, Hauth JC: Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity. Am J Obstet Gynecol 2004;191:1375–1381.
  17. Yoon BH, Romero R, Moon J, Chaiworapongsa T, Espinoza J, Kim YM, Edwin S, Kim JC, Camacho N, Bujold E, Gomez R: Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation. J Matern Fetal Neonatal Med 2003;13:32–38.
  18. Dembinski J, Behrendt D, Martini R, Heep A, Bartmann P: Modulation of pro- and anti-inflammatory cytokine production in very preterm infants. Cytokine 2003;21:200–206.
  19. Ng PC, Li K, Wong RP, Chui K, Wong E, Li G, Fok TF: Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fetal Neonatal Ed 2003;88:F209–F213.
  20. Stoll BJ, Hansen N, Fanaroff AA, et al: Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;110(2 Pt 1):285–291.
  21. Stoll BJ, Hansen N, Fanaroff AA, et al: Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 2002;347:240–247.
  22. Ahrne S, Nobaek S, Jeppsson B, Adlerberth I, Wold AE, Molin G: The normal Lactobacillus flora of healthy human rectal and oral mucosa. J Appl Microbiol 1998;85:88–94.
  23. Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS, Panigrahi P: Stool microflora in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1999;80:F167–F173.
  24. Hall MA, Cole CB, Smith SL, Fuller R, Rolles CJ: Factors influencing the presence of faecal lactobacilli in early infancy. Arch Dis Child 1990;65:185–188.
  25. Gronlund MM, Arvilommi H, Kero P, Lehtonen OP, Isolauri E: Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow-up study of healthy infants aged 0–6 months. Arch Dis Child Fetal Neonatal Ed 2000;83:F186–F192.
  26. Bayer AS, Chow AW, Betts D, Guze LB: Lactobacillemia – report of nine cases. Important clinical and therapeutic considerations. Am J Med 1978;64:808–813.
  27. Broughton RA, Gruber WC, Haffar AA, Baker CJ: Neonatal meningitis due to Lactobacillus. Pediatr Infect Dis 1983;2:382–384.
  28. Cox SM, Phillips LE, Mercer LJ, Stager CE, Waller S, Faro S: Lactobacillemia of amniotic fluid origin. Obstet Gynecol 1986;68:134–135.
  29. Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK: Lactobacillus sepsis associated with probiotic therapy. Pediatrics 2005;115:178–181.
  30. Lorenz RP, Appelbaum PC, Ward RM, Botti JJ: Chorioamnionitis and possible neonatal infection associated with Lactobacillus species. J Clin Microbiol 1982;16:558–561.
  31. Karlsson H, Larsson P, Wold AE, Rudin A: Pattern of cytokine responses to gram-positive and gram-negative commensal bacteria is profoundly changed when monocytes differentiate into dendritic cells. Infect Immun 2004;72:2671–2678.
  32. Hessle C, Andersson B, Wold AE: Gram-positive bacteria are potent inducers of monocytic interleukin-12 (IL-12) while gram-negative bacteria preferentially stimulate IL-10 production. Infect Immun 2000;68:3581–3586.
  33. Ellis S, Mouihate A, Pittman QJ: Early life immune challenge alters innate immune responses to lipopolysaccharide: implications for host defense as adults. FASEB J 2005;19:1519–1521.
  34. Schultz C, Rott C, Temming P, Schlenke P, Möller JC, Bucsky P: Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res 2002;51:317–322.
  35. Hebra A, Strange P, Egbert JM, Ali M, Mullinax A, Buchanan E: Intracellular cytokine production by fetal and adult monocytes. J Pediatr Surg 2001;36:1321–1326.
  36. Dembinski J, Behrendt D, Reinsberg J, Bartmann P: Endotoxin-stimulated production of IL-6 and IL-8 is increased in short-term cultures of whole blood from healthy term neonates. Cytokine 2002;18:116–119.
  37. Powell C, Orsi N, Simpson N, Levene M: Characterisation of the cytokine inflammatory response in LPS-stimulated full-term cord blood. J Perinat Med 2004;32:440–445.
  38. Hartel C, Adam N, Strunk T, Temming P, Müller-Steinhardt M, Schultz C: Cytokine responses correlate differentially with age in infancy and early childhood. Clin Exp Immunol 2005;142:446–453.
  39. Berner R, Csorba J, Brandis M: Different cytokine expression in cord blood mononuclear cells after stimulation with neonatal sepsis or colonizing strains of Streptococcus agalactiae. Pediatr Res 2001;49:691–697.
  40. La Pine TR, Joyner JL, Augustine NH, Kwak SD, Hill HR: Defective production of IL-18 and IL-12 by cord blood mononuclear cells influences the T helper-1 interferon gamma response to group B streptococci. Pediatr Res 2003;54:276–281.
  41. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG: IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 2001;166:5530–5539.
  42. Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S: Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr 2004;80:1618–1625.
  43. Cunningham-Rundles S: The effect of aging on mucosal host defense. J Nutr Health Aging 2004;8:20–25.
  44. Laborada G, Rego M, Jain A, Guliano M, Stavola J, Ballabh P, Krauss AN, Auld PA, Nesin M: Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis. Am J Perinatol 2003;20:491–501.
  45. Ng PC: Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004;89:F229–F235.

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