The Influence of Phototherapy on Serum Cytokine Concentrations in Newborn Infants

ABSTRACT

We sought to determine cytokine response in term and late preterm newborn infants on phototherapy. Twenty newborn infants with gestational age ≥35 weeks and birth weight ≥2000 g in the first week of life had serum interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor (TNF)-α measured immediately prior to and after 24 hours on phototherapy. Exclusion criteria were newborns with severe congenital malformations, congenital infections, birth asphyxia, sepsis, hemolytic anemia that required blood transfusion, maternal-infant Rh incompatibility and those who required exchange transfusion or intravenous immunoglobulin treatment for hyperbilirubinemia. Median IL-6 concentrations significantly decreased after 24 hours on phototherapy (18.3 pg/mL and 7.85 pg/mL, respectively, p = 0.005). IL-6 concentrations decreased in 17 out of the 20 newborns. There were no statistical differences in IL-8, IL-10, IL-1β, and TNF-α concentrations before and after 24 hours on phototherapy. There was a statistically significant correlation between IL-6 decline and irradiance (r = 0.57, p = 0.009). The finding that serum IL-6 decreases in newborn under phototherapy suggests that phototherapy possibly has an anti-inflammatory effect, although the clinical implications of this study deserve further studies.

KEYWORDS

Cytokines - hyperbilirubinemia - interleukin-6 - late preterm newborn - phototherapy

REFERENCES

• 1 Maisels M J, McDonagh A F. Phototherapy for neonatal jaundice.  N Engl J Med. 2008;  358 920-928
• 2 Aycicek A, Erel O. Total oxidant/antioxidant status in jaundiced newborns before and after phototherapy.  J Pediatr (Rio J). 2007;  83 319-322
• 3 Kumar A, Pant P, Basu S, Rao G R, Khanna H D. Oxidative stress in neonatal hyperbilirubinemia.  J Trop Pediatr. 2007;  53 69-71
• 4 Aycicek A, Kocyigit A, Erel O, Senturk H. Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants.  J Pediatr (Rio J). 2008;  84 141-146
• 5 Atabek M E, Pirgon O, Kurtoglu S et al.. Effects of phototherapy on the growth plate in newborn rats.  J Pediatr Orthop. 2006;  26 144-147
• 6 Matichard E, Le Hénanff A, Sanders A, Leguyadec J, Crickx B, Descamps V. Effect of neonatal phototherapy on melanocytic nevus count in children.  Arch Dermatol. 2006;  142 1599-1604
• 7 Cnattingius S, Zack M, Ekbom A, Gunnarskog J, Linet M, Adami H O. Prenatal and neonatal risk factors for childhood myeloid leukemia.  Cancer Epidemiol Biomarkers Prev. 1995;  4 441-445
• 8 Kurt A, Aygun A D, Kurt A NC, Godekmerdan A, Akarsu S, Yilmaz E. Use of phototherapy for neonatal hyperbilirubinemia affects cytokine production and lymphocyte subsets.  Neonatology. 2009;  95 262-266
• 9 Cohen M C, Cohen S. Cytokine function: a study in biologic diversity.  Am J Clin Pathol. 1996;  105 589-598
• 10 Arai K I, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T. Cytokines: coordinators of immune and inflammatory responses.  Annu Rev Biochem. 1990;  59 783-836
• 11 Harris M C, Costarino Jr A T, Sullivan J S et al.. Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis.  J Pediatr. 1994;  124 105-111
• 12 Kurt A N, Aygun A D, Godekmerdan A, Kurt A, Dogan Y, Yilmaz E. Serum IL-1beta, IL-6, IL-8, and TNF-alpha levels in early diagnosis and management of neonatal sepsis.  Mediators Inflamm. 2007;  2007 31397
• 13 Berner R, Niemeyer C M, Leititis J U et al.. Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis.  Pediatr Res. 1998;  44 469-477
• 14 Martin H, Olander B, Norman M. Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor-alpha in the diagnosis of early-onset neonatal sepsis.  Pediatrics. 2001;  108 E61
• 15 Silveira R C, Procianoy R S. Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis.  Acta Paediatr. 1999;  88 647-650
• 16 Santana Reyes C, García-Muñoz F G, Reyes D, González G, Dominguez C, Domenech E. Role of cytokines (interleukin-1beta, 6, 8, tumour necrosis factor-alpha, and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis.  Acta Paediatr. 2003;  92 221-227
• 17 Schwarz T, Luger T A. Effect of UV irradiation on epidermal cell cytokine production.  J Photochem Photobiol B. 1989;  4 1-13
• 18 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia . Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.  Pediatrics. 2004;  114 297-316
• 19 Sirota L, Straussberg R, Gurary N, Aloni D, Bessler H. Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells.  Eur J Pediatr. 1999;  158 910-913
• 20 Urbanski A, Schwarz T, Neuner P et al.. Ultraviolet light induces increased circulating interleukin-6 in humans.  J Invest Dermatol. 1990;  94 808-811
• 21 Kennedy M, Kim K H, Harten B et al.. Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells.  Invest Ophthalmol Vis Sci. 1997;  38 2483-2491
• 22 Chu R, Zheng X, Chen D, Hu D N. Blue light irradiation inhibits the production of HGF by human retinal pigment epithelium cells in vitro.  Photochem Photobiol. 2006;  82 1247-1250
• 23 Shnitkind E, Yaping E, Geen S, Shalita A R, Lee W L. Anti-inflammatory properties of narrow-band blue light.  J Drugs Dermatol. 2006;  5 605-610
• 24 Chiesa C, Signore F, Assumma M et al.. Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders.  Clin Chem. 2001;  47 1016-1022
• 25 Miller L C, Isa S, LoPreste G, Schaller J G, Dinarello C A. Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production.  J Pediatr. 1990;  117 961-965
• 26 Ambalavanan N, Carlo W A, D'Angio C T Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network et al. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants.  Pediatrics. 2009;  123 1132-1141
• 27 Wang M L, Dorer D J, Fleming M P, Catlin E A. Clinical outcomes of near-term infants.  Pediatrics. 2004;  114 372-376