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ORIGINAL ARTICLE
Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 189-192

The effect of neonatal phototherapy on serum level of interlukin-6 and white blood cells' count


Pediatric Growth Disorder Research Center, 17th Shahrivar Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Date of Web Publication28-Sep-2016

Correspondence Address:
Dr. Marjaneh Zarkesh
Pediatric Growth Disorder Research Center, 17th Shahrivar Hospital, Namjoo St., Rasht
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.191260

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  Abstract 

Introduction: Recent progress in medical sciences approved phototherapy (PT) as a standard method of treatment and care for hyperbilirubinemia in the neonatal period. Previous studies which assessed the effect of PT on serum cytokines levels and white blood cells' (WBCs) count in infants mentioned different results. The aim of this study was to investigate the effect of neonatal PT on serum level of interleukin-6 (IL) and WBCs' count in healthy neonates with hyperbilirubinemia. Materials and Methods: This is a cross-sectional analytic study, which was conducted on 97 term newborns admitted to 17 th Shahrivar Hospital, Rasht (Northern part of Iran), with the chief complaint of indirect hyperbilirubinemia. Data were gathered by a form, which consisted of demographic characteristics and laboratory results. Four lamps with a wavelength of 400-500 nm were used at a distance of 30 cm for PT. Blood samples were taken to measure WBCs' count and IL-6 level before and 48 h after PT. Data were analyzed by t-test and Pearson's correlation coefficient in SPSS 19 software. Results: The mean age of the infants was 6.82 ± 2.16 days and 62.9% were males. The mean amount of WBCs before and after PT was 9235 ± 2215 and 9700 ± 2163, respectively (P = 0.001). The mean level of IL-6 before and after PT was 1.14 ± 0.98 and 1.42 ± 1.17, respectively (P = 0.004). There was a positive correlation between WBCs' count and IL-6 levels before and after PT (P < 0.001). Conclusions: Our findings demonstrated that an increased level of serum IL-6 and WBCs' count in healthy term neonates after PT could be indicated as its complications. Therefore, it seems that PT can change the function of the neonatal immune system.

Keywords: IL-6, neonate, phototherapy, white blood cell


How to cite this article:
Zarkesh M, Dalili S, Fallah MJ, Heidarzadeh A, Rad AH. The effect of neonatal phototherapy on serum level of interlukin-6 and white blood cells' count. J Clin Neonatol 2016;5:189-92

How to cite this URL:
Zarkesh M, Dalili S, Fallah MJ, Heidarzadeh A, Rad AH. The effect of neonatal phototherapy on serum level of interlukin-6 and white blood cells' count. J Clin Neonatol [serial online] 2016 [cited 2019 Dec 15];5:189-92. Available from: http://www.jcnonweb.com/text.asp?2016/5/3/189/191260


  Introduction Top


Jaundice is a common disease, which commonly occurs in 60% of term neonates and indicates medical concerns in the neonatal period. It has been stated that hyperbilirubinemia that causes yellowish discoloration of the sclera and skin should be noted as jaundice.[1],[2] Recent progresses in medical sciences mentioned phototherapy (PT) as a standard method of treatment and care for jaundice in the neonatal period. PT uses the ultraviolet (UV) radiation that makes a surge of immune responses. Commonly, the immune system of the skin secretes a variety of immune mediator cytokines such as interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor-α to enhance the systemic immunologic responses.[3],[4] In addition, PT can have an effect on the peripheral immune system by changing the synthesis and release of cytokines. Cytokines can affect the growth, differentiation, and function of immune cells. They can be produced by various types of immune cells, especially T-cells and monocytes.[5] During infections, IL-6 as a proinflammatory cytokine can be produced. The positive blood culture in patients with sepsis can be commonly predicted by IL-6.[6] The primary function of IL-6 is its differentiation effect on activated B-cells, which enhances the antibody production.[7]

It was mentioned that PT also had an effect on cellular component of peripheral section of the immune system due to the accessibility to photons.[5] Previous investigation noted an increased peripheral white blood cells' (WBCs) count after exposure to UV radiation[8] However, Erduran et al. noted a significant decrease in WBCs consequent to PT.[9]

Despite the prolonged use of PT, its definite mechanism of action is unknown yet,[10] and different studies noted inconsistent results on cytokines' levels and WBCs' count after PT.[8] According to the high prevalence of hyperbilirubinemia and use of PT and also unknown complication, we decided to investigate the effect of PT on serum level of IL-6 and WBCs' count in healthy neonates with hyperbilirubinemia hospitalized in 17th Shahrivar Hospital, Rasht.

Procedure

This is a cross-sectional analytic study, which was conducted on term newborns admitted to 17th Shahrivar Hospital in Rasht (Northern province of Iran). Ninety-seven healthy infants aged <14 days with indirect hyperbilirubinemia participated in this study. Exclusion criteria were major congenital malformation, respiratory distress, sepsis, urinary tract infection, and <5,000 or >15,000/mm3 WBCs. In addition, neonates with a history of maternal diabetes, pre-eclampsia, and treatment with steroid and drug abuse were excluded from the study. Consent letters were obtained from parents. Data were gathered by a form that consisted of demographic characteristics and laboratory results. Four lamps for PT with a wavelength of 400-500 nm were used at a distance of 30 cm. Blood samples were taken to measure WBCs and IL-6 levels before and 48 h after PT. IL-6 level was measured by human cytokine kits  (Bender MedSystems). Researchers performed the laboratory assessment regarding the instructions in a single laboratory. All measurements were rechecked with a control kit. WBCs' count measurements with cell counter (ESI sysmex KX-21) were conducted in the single laboratory.

Data were reported by descriptive statistics such as frequency, percent, mean, standard deviation, and analyzed by paired sample t-test and Pearson's correlation coefficient in SPSS software Version 19. P <0.05 was considered statistically significant, and 95% confidence interval was noted.


  Results Top


Ninety-seven neonates including 61 (62.9%) males and 36 (37.1%) females with the mean age of 6.82 ± 2.16 days participated in the study. The results showed a statistically significant difference between WBCs' count before and after PT (P < 0.001) [Table 1].
Table 1: The effect of phototherapy on white blood cells count (number/m3)


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The mean level of IL-6 before and after PT was 1.14 ± 0.98 pg/dL and 1.42 ± 1.17 pg/dL, respectively (P = 0.004). In addition, the mean IL-6 levels after PT significantly increased in cases aged <7 days (P = 0.013) [Table 2].
Table 2: The effect of phototherapy on interleukin-6 level (pg/dl)


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The results indicated a positive correlation between WBCs' count and IL-6 levels before and after PT (P < 0.001) [Table 3].
Table 3: Correlation analysis


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  Discussion Top


PT is a standard method which can decrease bilirubin level and affect the neonatal immune system. As it is reported, after birth, T-helpers' (Th s) immune responses shift from Th -2 to Th -1. According to the previous investigation, PT can affect the Th -2:Th -1 switch. The equilibration between humoral (Th -2 cells) and cellular (Th -1 cells) immunity can have an impact on the immune competence.[11] IL-6 can also stimulate the differentiation of Th s to diverse subsets.[12] Although various animal researches have been conducted on the effect of UV radiation on the levels of inflammatory cytokines, there are some studies which assessed human beings recently.[13]

Sirota et al., who assessed fifty term neonates, reported that PT affects the function of the neonatal immune system by changing cytokine production. Whereas, no significant change in the level of IL-3 and IL-6 was mentioned.[5] Inconsistent with the previous study, Procianoy et al. who assessed twenty neonates with >35 weeks of gestation showed a decreased level of serum IL-6 in infants exposed to PT and reported an anti-inflammatory effect of PT.[14] Their results were not in agreement with that of ours. It seems that this difference might be because of smaller sample sizes and 24 h follow-up assessment in mentioned investigations. We noted a significant increase in the level of IL-6 consequent to PT during 48 h follow-up. In addition, Maisels and McDonagh demonstrated similar results. They reported elevated levels of IL-6, IL-8, and TNF-α after UV radiation for neonatal jaundice.[15]

In 2014, Beken et al. stated no significant difference between the blood cell count including leukocytes, lymphocytes, neutrophils, and platelets, before and after PT, but elevated eosinophil levels were noted. Therefore, they mentioned allergic diseases in later life according to higher levels of eosinophils in the neonatal period.[16] Mrkaic et al. studied the effects of PT on the immune system of neonates without signs of infection, anoxia, and birth injury. Their results showed a raise in the amount of peripheral WBCs, polymorphonuclears, lymphocytes, and monocytes as well as a delay in the chemiluminescence response of the peripheral blood phagocytes.[17] Jahanshahifard et al. demonstrated that PT might increase the peripheral WBCs' count considerably. Their results were similar with ours. They reported that this increase was unspecific and might be because of admission stress or beginning of infection.[8] In contrast with our study, Erduran et al. showed a significant decrease in WBCs' count after exposure to UV radiation.[9] Furthermore, Saber et al. observed no statistically significant difference in WBCs' count before and after PT.[3]

Our results indicated a significant difference between WBCs' count and IL-6 levels before and after PT regarding age groups. However, there was no published study which compared the results based on age.


  Conclusions Top


Our findings demonstrated that increased level of serum IL-6 levels and WBCs' count in healthy term neonates after PT might be indicated as its complications. Therefore, it seems that PT can change the function of the infantile immune system.

Acknowledgments

This investigation was based on the thesis submitted by the third author (Maryam Jamalzadeh Fallah) to the Guyan University of Medical Sciences.

Financial support and sponsorship

This study was financially supported by the Vice chancellor of research in the Guilan University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Dhanjal GS. Clinico-etiological study of neonatal jaundice in a tertiary carecentre in Ambala (Haryana) India. J Biomed Pharm Res 2014;3:64-7.  Back to cited text no. 1
    
2.
Hansen TW. Bilirubin oxidation in brain. Mol Genet Metab 2000;71:411-7.  Back to cited text no. 2
[PUBMED]    
3.
Saber M, Abd El Naby S, Helwa M, Deghedy R. The influence of phototherapy for neonatal hyperbilirubinemia on tumour necrosis factor-α. Menoufia Med J 2014;27:44.  Back to cited text no. 3
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4.
Narbutt J, Lesiak A, Skibinska M, Wozniacka A, Sysa-Jedrzejowska A, Lukamowicz J, et al. Repeated doses of UVR cause minor alteration in cytokine serum levels in humans. Mediators Inflamm 2005;2005:298-303.  Back to cited text no. 4
[PUBMED]    
5.
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;158:910-3.  Back to cited text no. 5
[PUBMED]    
6.
Ding Y, Lin Y, Zhu T, Huang M, Xu Q. Interleukin 6 increases dysfunction of organs in sepsis rats through sirtuin 1. Int J Clin Exp Med 2014;7:2593-8.  Back to cited text no. 6
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7.
Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: Mechanisms of production and implications in disease. FASEB J 2001;15:43-58.  Back to cited text no. 7
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8.
Jahanshahifard S, Ahmadpour-Kacho M, Pasha YZ. Effects of phototherapy on cytokines′ levels and white blood cells in term neonate with hyperbilirubinemia. J Clin Neonatol 2012;1:139-42.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
9.
Erduran E, Arslan M, Alperen A, Tekelioglu Y. In vitro investigation of the effect of ultraviolet-C light on lymphocytes. Turk Hematol Onkol Derg 1997;7:30-2.  Back to cited text no. 9
    
10.
Weichenthal M, Schwarz T. Phototherapy: How does UV work? Photodermatol Photoimmunol Photomed 2005;21:260-6.  Back to cited text no. 10
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11.
Bjorksten B, editor. Environmental Influences on the Development of the Immune System: Consequences for Disease Outcome. Nestle Nutr Workshop Ser Pediatr Program; 2008.  Back to cited text no. 11
    
12.
Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin′s Neonatal-perinatal Medicine: Diseases of the Fetus and Infant . Philadelphia: Elsevier Health Sciences; 2014.  Back to cited text no. 12
    
13.
Kurt A, Aygun AD, Kurt AN, Godekmerdan A, Akarsu S, Yilmaz E. Use of phototherapy for neonatal hyperbilirubinemia affects cytokine production and lymphocyte subsets. Neonatology 2009;95:262-6.  Back to cited text no. 13
    
14.
Procianoy RS, Silveira RC, Fonseca LT, Heidemann LA, Neto EC. The influence of phototherapy on serum cytokine concentrations in newborn infants. Am J Perinatol 2010;27:375-9.  Back to cited text no. 14
[PUBMED]    
15.
Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med 2008;358:920-8.  Back to cited text no. 15
[PUBMED]    
16.
Beken S, Aydin B, Zencirogglu A, Dilli D, Özkan E, Dursun A, et al. The effects of phototherapy on eosinophil and eosinophilic cationic protein in newborns with hyperbilirubinemia. Fetal Pediatr Pathol 2014;33:151-6.  Back to cited text no. 16
    
17.
Mrkaic LJ, Kamenov B, Najman S, Dimitrijevic H, Mitrovic V, Maglajlic S. Neonatal immune system changes caused by phototherapy. Srp Arh Celok Lek 1994;122 Suppl 1:36-7.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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