|Year : 2019 | Volume
| Issue : 4 | Page : 249-252
Study of serum interleukin 5 level and factors that impact on this level in Iraqi asthmatic children
Raghdah Maytham Hameed1, Haidar Abdul Amir Najim Abood2, Mohanad Mohsin Ahmed1, Aqeel Mahdi Hussein3
1 Department of Medical Microbiology, University of Kerbala, Karbala, Iraq
2 Department of Pharmacology, University of Kerbala, Karbala, Iraq
3 Department of Consultant Pediatrician, Karbala Teaching Hospital for Children, Karbala, Iraq
|Date of Submission||26-Aug-2019|
|Date of Acceptance||28-Sep-2019|
|Date of Web Publication||03-Dec-2019|
Ms. Raghdah Maytham Hameed
Department of Medical Microbiology, University of Kerbala, Kerbala
Source of Support: None, Conflict of Interest: None
Background: Interleukin-5 (IL-5) is a cytokine associated with the cause of several allergic diseases such as asthma due to their function in growth, activation, and maturation of eosinophils and stimulates B-cell growth and increases immunoglobulin E (IgE) secretion. The study aims to measure the IL-5 level in asthmatic children and detect the relationship between IL-5 level with eosinophils, total serum IgE level, and asthma severity. Methods: Eighty asthmatic children, including 55 males and 25 females with asthma who aged between 1 and 16 years collected at Kerbala Teaching Hospital for Children, were measured IL-5 level using Elabscience ELISA kit and measured total IgE level using EUROIMMUN IgE ELISA kit. However, absolute eosinophils count was examined by peripheral blood smear. In addition, the clinical characteristics of the patients were recorded by a questionnaire. Results: There was a significant difference in IL-5 level in asthma patients depending on sex, absolute eosinophil count, and use of treatment (P = 0.046, 0.046, and 0.001, respectively). However, there was no effect on the IL-5 level at asthmatic children depending on the age, body mass index, resident, exposure to cigarette smoking, family history of asthma/allergic diseases, asthma severity, and total serum IgE (P = 0.936, 0.769, 0.154, 0.898, 0.614, 0.550, and 0.874, respectively). Conclusions: IL-5 level had a positive correlation with absolute eosinophils count but not with total serum IgE. In addition, IL-5 level was a poor indicator of asthma severity.
Keywords: Asthma, eosinophil, interleukin 5, total serum immunoglobulin E
|How to cite this article:|
Hameed RM, Abood HA, Ahmed MM, Hussein AM. Study of serum interleukin 5 level and factors that impact on this level in Iraqi asthmatic children. Biomed Biotechnol Res J 2019;3:249-52
|How to cite this URL:|
Hameed RM, Abood HA, Ahmed MM, Hussein AM. Study of serum interleukin 5 level and factors that impact on this level in Iraqi asthmatic children. Biomed Biotechnol Res J [serial online] 2019 [cited 2021 Oct 18];3:249-52. Available from: https://www.bmbtrj.org/text.asp?2019/3/4/249/272187
| Introduction|| |
Asthma is the most common chronic lower respiratory tract and noncommunicable diseases in children and adults throughout the world, characterized by inflammation which affects both proximal and distal airways.,,,, It is a highly prevalent chronic inflammatory disease of the airways, with differences in etiology, immunologic mechanisms, clinical presentation, pathogenesis, comorbidities, prognosis, and response to treatment. Asthma is primarily an inflammatory disorder of the airways associated with T-helper type 2 (Th2), cell-dependent promotion of immunoglobulin E (IgE) production, and recruitment of mast cells and eosinophils. Allergic asthma may involve adaptive and innate, antigen-independent immune responses. Th2-type cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, are thought to drive the disease pathology in patients with asthma and play a role in driving many of the hallmarks of allergic inflammation., IL-5 is the critical molecular switch for developing, migrating, and recruiting eosinophils to the lung during allergic inflammation., IL-5 exerts its biological actions via stimulation of the IL-5 receptor expressed by eosinophils, and to a lesser extent, also by basophils.
IL-5 is an interdigitation homodimeric glycoprotein. IL-5 is produced by both hematopoietic and nonhematopoietic cells, including T-cells, granulocytes, and natural helper cells. IL-5 regulates the growth, differentiation, and activation of eosinophils. In addition, overexpression of IL-5 significantly increases antibody levelsin vivo and is reported to act as a B-cell differentiation factor by stimulating activated B-cells to secrete antibody.,
The study protocol was approved by the Ethical Committee in the Kerbala Health Directorate. In addition, verbal approval was taken from the patients and/or their parents before taking the sample. Health measures and safety were taken when sampling.
| Methods|| |
A cross-sectional study was carried out at Karbala Teaching Hospital for Children; the study was conducted from October 2018 to December 2018 and included 80 asthmatic children (55 males and 25 females, aged between 1 and 16 years). All children in this study were diagnosed as asthmatic patients by a clinician. A questionnaire was framed for collecting the information and clinical data from patients or their parents.
Sample collection and processing
Sera were used to determine the serum IL-5 and total serum IgE levels by BioTek ELX800 automated immunoassay analyzer (BioTek, USA) using Elabscience ELISA kit (LOT NO. 4CN1IPT94C) and EUROIMMUN total IgE ELISA kit (LOT NO. A180417AC), respectively. While, whole blood was used for total and differential white blood cells' count that was measured by Sysmex XN-350 five differential automated hematology analyzer (Sysmex, Japan). Differential leukocyte count was displayed in percentage. Therefore, the absolute eosinophil count was measured by the following equation: Absolute eosinophil count = (WBC × eosinophils%)/100.
Data were introduced into a specific software Statistical Package for the Social Sciences version 21 for Windows (GraphPad Software, San Diego, California, USA) to do the statistical analysis. The results were expressed as mean ± standard deviation. Comparisons between two means were performed using t-test, while ANOVA was using to compare among mean. A P< 0.05 was considered to indicate the statistical significance and highly significant if P < 0.001.
| Results|| |
[Table 1] shows the demographic and biochemical profile of asthmatic children. Comparison between demographic pictures, clinical characteristics, and immunological parameters of asthmatic children in IL-5 levels is presented in [Table 2].
|Table 2: Comparison between demographic pictures, clinical characteristics, and immunological parameters of asthmatic children in interleukin-5 levels|
Click here to view
Further, in this study, there was a significant difference in the IL-5 level in asthma patients depending on sex, absolute eosinophil count, and use of treatment (P = 0.046, 0.046, and 0.001, respectively). However, there was no effect on IL-5 level at asthmatic children depending on the age, body mass index, resident, exposure to cigarette smoking, family history of asthma/allergic diseases, asthma severity, and total serum IgE (P = 0.936, 0.769, 0.154, 0.898, 0.614, 0.550, and 0.874 respectively), as shown in [Table 2].
| Discussion|| |
IL-5 is thought to have an important role in the pathogenesis of asthma and prominent feature of airway inflammation in asthma due to their ability to regulate the growth, activation, and survival of eosinophils.,,,
The current study shows a significant correlation between serum IL-5 levels and absolute eosinophil count in asthmatic children (P = 0.045). The result agrees with the previous study, who mentioned that a robust relationship between blood eosinophilia and IL-5. In addition, Kuo et al. and Kouro and Takatsu, concluded that there was increased expression of IL-5 of patients with asthma and this expression may autoregulate eosinophil and increase eosinophil numbers. Other researchers found that the biologic effects of IL-5 were best characterized by eosinophils. This result is because IL-5 is the key cytokine responsible for maturation, activation, proliferation, and survival of eosinophils. IL-5 is responsible for the maturation and release of eosinophils in the bone marrow. IL-5 is a critical regulator of eosinophilia and has effects on eosinophil progenitors. In addition, IL-5 acts on eosinophils at multiple functional levels and time points during their life span.
The study shows no significant correlation between IL-5 levels and total serum IgE in asthmatic children (P = 0.874). The result agrees with other previous results, who mentioned that IL-5 alone was not enough to induce IgE production.,, Deo et al. confirmed the importance of IL-5 in eosinophilic inflammation but no correlation between IL-5 levels and IgE in asthma (P = 0.13). In contrast, another study showed that IL-5 production was associated within vivo total IgE levels in an infant.
This study shows that the serum IL-5 levels were 32.4 pg/ml in moderate asthma while 31.2 pg/ml in mild asthma. This result agrees with previous study, who mentioned that IL-5 levels elevated in mild and moderate asthma, but there was a tendency for serum IL-5 levels to be higher in moderate asthmatic children compared to mild asthmatic children. The serum IL-5 levels had no highly significant difference between mild and moderate asthma (high levels in mild and moderate) because IL-5 could have contributed to airway smooth muscle hyperresponsiveness and airway inflammation and this result is as same as another previous study. Moreover, Huang et al. mentioned that serum IL-5 levels were a poor indicator of disease activity in acute asthma. The presence of IL-5 might be more relevant to the pathogenesis of asthma but not be closely reflected asthma severity. This finding is also consistent with the present study.
Higher serum IL-5 levels might relate to obesity in patients with asthma,, while the current study disagrees with previous study. There was no significant associated between high mean of IL-5 levels and obesity in asthmatic children. The present study shows no significant difference in IL-5 level between asthmatic patients who exposed to smoking and patients not exposed, but on the contrary, Krisiukeniene et al. reported higher IL-5 levels found in asthmatic patients who never smoked.
The results of the study reveal that the level of IL-5 in asthmatic children on controller therapy was lower than the level in patients without controller (25.2 ml and 36.8 pg/ml respectively, P < 0.001). This result agrees with other previous studies, who mentioned that after montelukast therapy for 7 days, the levels of IL-5 in patients were significantly decreased., The cause of IL-5 level reduction is that montelukast can regulate the Th1/Th2 balance, block IL-5 mRNA expression, and improve the airway inflammation caused by acute bronchial asthma (BA) and the clinical symptoms and lung function of patients with acute BA.
| Conclusions|| |
IL-5 has an important role in asthma pathogenesis through activation, maturation, and attraction of eosinophils. IL-5 level has a positive correlation with absolute eosinophils count but not with total serum IgE levels. Further, IL-5 level was high in both mild and moderate asthma. The use of montelukast treatment may reduce IL-5 level.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Beasley R, Semprini A, Mitchell EA. Risk factors for asthma: Is prevention possible? Lancet 2015;386:1075-85.
Fu LS, Tsai MC. Asthma exacerbation in children: A practical review. Pediatr Neonatol 2014;55:83-91.
Looijmans-van den Akker I, van Luijn K, Verheij T. Overdiagnosis of asthma in children in primary care: A retrospective analysis. Br J Gen Pract 2016;66:e152-7.
Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet 2018;391:783-800.
Perez T, Chanez P, Dusser D, Devillier P. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respir Med 2013;107:1667-74.
Mims JW, editor. Asthma: Definitions and Pathophysiology. Int Forum Allergy Rhinol 2015;5 Suppl 1:S2-6.
Holgate ST. Innate and adaptive immune responses in asthma. Nat Med 2012;18:673-83.
Suarez CJ, Parker NJ, Finn PW. Innate immune mechanism in allergic asthma. Curr Allergy Asthma Rep 2008;8:451-9.
Georas SN, Guo J, De Fanis U, Casolaro V. T-helper cell type-2 regulation in allergic disease. Eur Respir J 2005;26:1119-37.
Lloyd CM, Hessel EM. Functions of T cells in asthma: More than just T(H)2 cells. Nat Rev Immunol 2010;10:838-48.
Tomasiak-Łozowska MM, Bodzenta-Łukaszyk A, Tomasiak M, Skiepko R, Zietkowski Z. The role of interleukin 13 and interleukin 5 in asthma. Postepy Hig Med Dosw (Online) 2010;64:146-55.
Possa SS, Leick EA, Prado CM, Martins MA, Tibério IF. Eosinophilic inflammation in allergic asthma. Front Pharmacol 2013;4:46.
Greenfeder S, Umland SP, Cuss FM, Chapman RW, Egan RW. Th2 cytokines and asthma. The role of interleukin-5 in allergic eosinophilic disease. Respir Res 2001;2:71-9.
Takatsu K, Kouro T, Nagai Y. Interleukin 5 in the link between the innate and acquired immune response. Adv Immunol 2009;101:191-236.
Takatsu K. Interleukin-5 and IL-5 receptor in health and diseases. Proc Jpn Acad Ser B Phys Biol Sci 2011;87:463-85.
Matthaei KI, Foster P, Young IG. The role of interleukin-5 (IL-5) in vivo
: Studies with IL-5 deficient mice. Mem Inst Oswaldo Cruz 1997;92 Suppl 2:63-8.
Kouro T, Takatsu K. IL-5- and eosinophil-mediated inflammation: From discovery to therapy. Int Immunol 2009;21:1303-9.
Randall TD, Lund FE, Brewer JW, Aldridge C, Wall R, Corley RB. Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation. Mol Cell Biol 1993;13:3929-36.
Joseph J, Benedict S, Safa W, Joseph M. Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy. BMC Pulm Med 2004;4:2.
Nag SS, Xu LJ, Hamid Q, Renzi PM. The effects of IL-5 on airway physiology and inflammation in rats. J Allergy Clin Immunol 2003;111:558-66.
Adachi T, Alam R. The mechanism of IL-5 signal transduction. Am J Physiol 1998;275:C623-33.
Takatsu K, Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol 2008;20:288-94.
Agache I, Strasser DS, Klenk A, Agache C, Farine H, Ciobanu C, et al.
Serum IL-5 and IL-13 consistently serve as the best predictors for the blood eosinophilia phenotype in adult asthmatics. Allergy 2016;71:1192-202.
Kuo HP, Wang CH, Lin HC, Hwang KS, Liu SL, Chung KF. Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: Effect of glucocorticoids. Br J Pharmacol 2001;134:1539-47.
Pelaia C, Vatrella A, Busceti MT, Gallelli L, Terracciano R, Savino R, et al.
Severe eosinophilic asthma: From the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des Devel Ther 2017;11:3137-44.
Fulkerson PC, Schollaert KL, Bouffi C, Rothenberg ME. IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation. J Immunol 2014;193:4043-52.
Rothenberg ME, Hogan SP. The eosinophil. Annual review of immunology 2006;24:147-74.
Pène J, Rousset F, Brière F, Chrétien I, Wideman J, Bonnefoy JY, et al.
Interleukin 5 enhances interleukin 4-induced IgE production by normal human B cells. The role of soluble CD23 antigen. Eur J Immunol 1988;18:929-35.
Manise M, Holtappels G, Van Crombruggen K, Schleich F, Bachert C, Louis R. Sputum IgE and cytokines in asthma: Relationship with sputum cellular profile. PLoS One 2013;8:e58388.
Grund LZ, Komegae EN, Lopes-Ferreira M, Lima C. IL-5 and IL-17A are critical for the chronic IgE response and differentiation of long-lived antibody-secreting cells in inflamed tissues. Cytokine 2012;59:335-51.
Deo SS, Mistry KJ, Kakade AM, Niphadkar PV. Role played by Th2 type cytokines in IgE mediated allergy and asthma. Lung India 2010;27:66-71.
] [Full text]
Crestani E, Lohman IC, Guerra S, Wright AL, Halonen M. Association of IL-5 cytokine production andin vivo
IgE levels in infants and parents. J Allergy Clin Immunol 2007;120:820-6.
Alexander AG, Barkans J, Moqbel R, Barnes NC, Kay AB, Corrigan CJ, et al.
Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma. Thorax 1994;49:1231-3.
Huang CS, Chen SJ, Chung RL, Tang RB. Serum interleukin-5 measurements for monitoring acute asthma in children. J Asthma 2005;42:297-300.
Marijsse GS, Seys SF, Schelpe AS, Dilissen E, Goeminne P, Dupont LJ, et al.
Obese individuals with asthma preferentially have a high IL-5/IL-17A/IL-25 sputum inflammatory pattern. Am J Respir Crit Care Med 2014;189:1284-5.
Wala'a EJ, Batool AA, Yacoob YA. Association between interleukin-5 and Body mass index among Iraqi asthmatic patients. J Fac Med 2007;116:49-20.
Krisiukeniene A, Babusyte A, Stravinskaite K, Lotvall J, Sakalauskas R, Sitkauskiene B. Smoking affects eotaxin levels in asthma patients. J Asthma Official J Assoc Care Asthma 2009;46:470-6.
Frieri M, Therattil J, Wang SF, Huang CY, Wang YC. Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma. Allergy Asthma Proc 2003;24:359-66.
Qu X, Chen Y, Yin C. Effect of montelukast on the expression of CD4(+) CD25(+) regulatory T cells in children with acute bronchial asthma. Exp Ther Med 2018;16:2381-6.
[Table 1], [Table 2]