The spatial distribution of interleukin-4 (IL-4) reference values in China based on a back propagation (BP) neural network

Submitted: 23 March 2023
Accepted: 27 August 2023
Published: 13 September 2023
Abstract Views: 833
PDF: 290
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


This study aimed to investigate the geospatial distribution of normal reference values of Interleukin 4 (IL-4) in healthy Chinese adults and to provide a basis for the development of standard references. IL-4 values of 5,221 healthy adults from 64 cities in China were collected and analyzed for a potential correlation with 24 topographical, climatic and soil factors. Seven of these factors were extracted and used to build a back propagation (BP) neural network model that was used to predict IL-4 reference values in healthy individuals from 2,317 observation sites nationwide. The predicted values were tested for normality and geographic distribution by analytic Kriging interpolation to map the geographic distribution of IL-4 reference values in healthy Chinese subjects. The results showed that IL-4 values generally decreased and then increased from the South to the North. We concluded that the BP neural network model applies to this approach, where certain geographical factors determine levels of various biochemical and immunological standards in healthy adults in regions with different topography, climate and soil indices.



PlumX Metrics


Download data is not yet available.


Braun C, Vocanson M, Nicolas JF, Nosbaum A, 2020. Pathophysiology of atopic dermatitis and other atopic diseases: is a global approach possible? Ann Dermatol Venereol 147:11S4-11S11 DOI:
Chen YG, 2009. Development of spatial autocorrelation theory and methodological improvements based on Moran statistics. Geogr Stud 28:1449-63.
Davis MS, Williams CC, Meinkoth JH, Malayer JR, Royer CM, Williamson KK, McKenzie, EC, 2007. Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air. Am J Vet Res 68:185-9. DOI:
Ding XS, 2010. Spatial and temporal distribution characteristics of high temperature heat waves in Jiangsu Province and their impact on human health, Vol. Master. Nanjing University of Information Engineering. Nanjing Univ Inf Eng. pp. 72.
Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M, 2013. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab 17:860-72. DOI:
Facco M, Zilli C, Siviero M, Ermolao A, Travain, G, Baesso I, Bonamico S, Cabrelle A, Zaccaria M, Agostini C, 2005. Modulation of immune response by the acute and chronic exposure to high altitude. Med Sci Sports Exerc 37:768-74. DOI:
Feng J, Chen TH, Dai LF, Tang N, Du W, Ye XG, Lei SG, 2022. Bivariate spatial autocorrelation analysis of influenza vaccination rate and socioeconomic indicators among children aged 6 months-5 years in Guizhou Province during the influenza season of 2020-2021. Vac Im Chin 28:199-203.
Ge Y, Yao S, Pu YX, Jia L,2005. A bivariate spatial autocorrelation analysis of influenza vaccination rates and socioeconomic indicators for children aged 5 months in China. Geographical patterns of agglomeration economic types using spatial autocorrelation analysis. Hum Geogr 03:21-25. [in Chinese]
Gu SQ, 2016. Alterations in lymphocyte subpopulations, platelets and coagulation function in healthy individuals at different altitudes. Chin J Blood Trans 29:700-703.
Guo HY, Wang DX, 2018. Comparison of serum IL-2, IL-4, TNF-α, CRP dynamic levels and recovery time of gastrointestinal function in elderly patients with acute cholecystitis under different surgical approaches. Mark Im Clin 25:94-98.
Hong MY, Yu HW, Zhu Y, JL, Z C, Z YL, Wang WY, 2022. Effects of acupuncture on the ultrastructure of synovial cells and IL-1β, IL-4 and IL-10 in rats with rheumatoid arthritis model. J Gansu Univ Trad Chin Med 39:9-12.
Hou B, 2014. Clinical study of the relationship between serum IL-2 and IL-4 and chronic obstructive pulmonary disease at different altitudes. Qinghai Univ. [in Chinese] (That's all the information I can find on this article, it's a dissertation)
Huang WQ, Li H, Yuan M, Chen SD, 2015. Changes in the levels of peripheral blood T-cell subsets Th1, Th2 and their related cytokines in patients with bronchial asthma and their significance. Shandong Med 55:40-41.
Ji J, Zhang RP, Yan J, Song T, Xu P, 2020. Effect of tacrolimus combined with compound glycopyrrolate tablets on serum Th1/Th2 type cytokine levels in patients with stable vitiligo. Chin Aes Med 29: 48-51. [in Chinese]
Jiang QW, Zhao F, 2011. Application of spatial autocorrelation analysis method in epidemiology. Chin J Epidemiol 32:539-546.
Lan X, Li ZM, Zhang WD, 2018. Determination of the reference range of serum inflammatory cytokines in a normal population in Zhengzhou. J Zhengzhou Univ 53:341-343.
Li JX, Li ZQ, Yin W, 2013. Kriging interpolation method based on ArcGIS and its application. Mapping Bul 09: 87-90. [in Chinese]
Li L, Xu Y, 2021. Building energy consumption prediction based on BP neural network. Com Prog Skills Main 04 :10-12. [in Chinese]
Li L, Zhao W, Wang ZF, 2006. Superiority of ridge regression method over LS method in solving multicollinearity problems. J Bohai Univ (Natural Science Edition) 02: 124-126. [in Chinese]
Li SQ, 2013. Effects of lead and cadmium pollution and p53 gene polymorphisms on the serum levels of related factors in the Sha Ying River area. J Zhengzhou Univ 48:788-791.
Liang JY, Feng CJ, Song P, 2016. A review of big data correlation analysis. J Com Science 39:1-18.
Liu GM, Wang YA, Zhang HR, Wang D, 2011. Several interpolations in spatial analysis. A comparative study of several interpolation methods in spatial analysis. Geog Inf World 9:41-45.
Liu J, Jin YY, Sun BQ, Yang J, 2019. Distribution pattern of TCM body quality in 1336 residents in Kunshan area. Shanxi Trad Chin Med 35:50-52.
Liu M, 2013. Resolution of multicollinearity: a new criterion for eliminating variables. Stat Dec Making 05: 82-83. [in Chinese]
Liu T, Yao ML, Huang JG, Huang SQ, Chen HY, Yang WW, Cai J, Wu R, 2021. Comparison of the prediction effectiveness of BPNN neural network model and SARIMA model in the incidence number of class B infectious diseases in Jingzhou City. Chin J Soc Med 38:109-113.
Liu YY, Li JC, 2016. Comparison of spatial interpolation methods for atmospheric PM_(2.5) concentration distribution in Changsha City. Env Mon Man Tech 28:14-18.
Luo W, ZJ, WZ, 2021. Circulating levels of IL‐2, IL‐4, TNF‐α, IFN‐γ, and C‐reactive protein are not associated with severity of COVID‐19 symptoms. J Med Virol 93:89-91. DOI:
Ma JH, 1992. Re-understanding of soil distribution laws. J Henan Univ (Natural Science Edition) 1: 1-5. [in Chinese]
Ma YP, Huang JF, Li CX, Qiu EC, Yu HB, Qi XL, Li HL, 2016. Analysis of injury and disease occurrence during plateau training in a department in Xinjiang. J Pla Prev Med 34:401-403.
Meng Y, Weng XQ, Yuan Y, 2015. Effects of acute exercise of different intensities on body T lymphocytes and their subpopulations in humid and hot environment, 2015 10th Nat Sports Science Conf, Hangzhou, Zhejiang, China. pp. 2.
Miao ZL, Zhong XM, Cui R, Li PP, Wang YX, Zhong WY, Zhao WZ, 2020. Effect of specimen storage time and temperature on Th1/Th2 intracellular cytokine assay by stimulation method. Guangdong Med 41:2522-2525. [in Chinese]
Min JW, Park S-M, Rhim TY, Park S-W, Jang A-S, Uh S-T, Park C-S, Chung IY, 2007. Effect and mechanism of lipopolyeac-charide on allergen-induced interleukin-5 and eotaxins produciton by whole blood cultures of atopic asthmaitcs. Clin Exp Immunol 147:440-8. DOI:
Monteiro MF, Casati MZ, Sallum EA, Silvério KG, Nociti-Jr FH, Casarin RCV, 2022. The familial trend of the local inflammatory response in periodontal disease. Oral Dis 28:202-209. DOI:
Nguyen JL, Yang W, Ito K, Matte TD, Shaman J, Kinney PL, 2016. Seasonal Influenza Infections and Cardiovascular Disease Mortality. JAMA Cardiol 1:274-281. DOI:
Nie Y, Luo Y, Yu J, Chen F, 2013. Spatial autocorrelation-based spatial and temporal evolution characteristics of arable land pressure in Hubei Province. Geogr Res Dev 32:112-116.
Niu HQ, Xu MH, Wang RB, Li XF, 2022. Progress on the regulation of intestinal flora and immune function by diet and its role in rheumatoid arthritis. Chin J Rheumatol 26:262-266.
Oliver MA, Webster R, 1990. Kriging: a method of interpolation for geographical information systems. Intl J Geogr Inf Syst 4:313-332. DOI:
Pang YH, Zheng CQ, Wang YC, Li XD, Li F, 2005. Expression of IL-4 and IL-13 in ulcerative colitis. J Gastroenterol Hepatol 143:410-412.
te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG, 1990. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood 76:1392-7. DOI:
Tomar S, Ganesan V, Sharma A, Zeng C, Waggoner L, Smith A, Chang H Kim CH et al., 2021. lL-4-BATF signaling directly modulates Il-9 producing mucosal mast cell (MMC9) function in experimental food allergy. J Allergy Clin Immunol 147:280-95. DOI:
Valero M, Li F, Clemente J, Song W, 2019. Distributed and Communication-Efficient Spatial Auto-Correlation Subsurface Imaging in Sensor Networks. Sensors (Basel) 19:2427. DOI:
Wang CC, Wu JH, ZhouY, Peng YB, Cao YZ, Song Y, Zhang XY, Yuan X, Wang Q, Wang GL, 2018. A study on the risk prediction of spontaneous hemorrhagic transformation in patients with acute cerebral infarction based on BP neural network. Chin Fam Med 21:1413-1418.
Wang G, Li J, Huang S, 2020. Immunofluorescence localization of CD14, IL-4 and TNF-α in tissues of healthy subjects and patients with chronic periapical disease. Chin J Pathophysiol 36: 539-546. [in Chinese]
Wang HL, Chen WJ, He J, Li CL, Liu JW, 2020. Expression and significance of T-cell subsets in patients with common psoriasis in a plateau environment in Xinjiang. Xinjiang Med 50:1256-1259.
Wang T, Chen PJ, Gao BH, 2006. Changes in peripheral blood leukocyte gamma-interferon, interleukin-4 and perforin gene expression before and after hypoxic training in female rowers. Chin J Sports Med 25: 196-199. [in Chinese]
Wei HY, 2019. Diagnosis and treatment of multicollinearity in regression analysis. J Zhoukou Norm Coll 36:11-15.
Wei J, Shang T, Wang DZ, 2003. Imbalance of Th1 and Th2 cytokine production by peripheral blood mononuclear cells in patients with gestational hypertension syndrome. Chin J Per Med 4: 4-7. [in Chinese]
Yang J, Duan XY, Huang T, He JB, Jia YC, Guo H, Peng X, Zheng ERD, 2020. Spatial and temporal epidemiological characteristics of hand, foot and mouth disease in Yunnan Province, 2014-2018. Chin J Dis Contr 24:290-296.
Yang Q, Tang QH, Zhang YY, 2019. Spatial and temporal characteristics of water quality in the Huaihe River Basin (Henan section) and its relationship with land use types. Env Science Res 32:1519-1530.
Yang X, Xu G, Li Q, Guo Y, Zhang M, 2017. Authorship attribution of source code by using back propagation neural network based on particle swarm optimization. PLoS ONE 12:e187204. DOI:
Yue WZ, Xu JH, Xu LH, 2005. Spatial interpolation of climate elements based on geostatistical methods. Highl Met 06: 974-980. [in Chinese]
Zahedi A, Hassanvand MS, Jaafarzadeh N, Ghadiri A, Shamsipour AM, Dehcheshmeh MG, 2021. Effect of ambient air PM2. 5-bound heavy metals on blood metal (loid) s and children’s asthma and allergy pro-inflammatory (IgE, IL-4 and IL-13) biomarkers. J Trace Elem Med Bio 68:126826. DOI:
Zhang HX, Niu SHW, Qi JH, Ye LQ, Li N, 2016. Geostatistical analysis of population distribution in Henan Province based on township scale. Geogr Stud 35:325-336.
Zhang J, Liang X, Liu YF, Zhang X, Sun LQ, Zhao F, Fu PY, 2021. Spatial distribution prediction of arsenic in groundwater based on principal component co-kriging method. Earth Science 1-22. [in Chinese]
Zhou ZS, Ji ZQ, Zhu XJ, Wang YQ, Xue WL, Tao HW, Jiang WQ, Liang WH, 2014. Correlation of rs3024608, rs1110470, and rs3024685 polymorphisms of IL-4R gene with metacarpal atopic signs in asthmatic patients with large fissure. Chin J Trad Chin Med 29:1076-1079.
Zhu HB, He LJ, 2009. A study on the conditions of consistency test for normal distribution etc. using single sample K-S test in SPSS. J Cap Inst Phy Educ 21:466-470.
Zhu QA, Zhang WC, Yu JH, 2004. A study of GIS-based spatial interpolation method. J Jiangxi Norm Univ (Natural Science Edition) 02: 183-188. [in Chinese]

How to Cite

Huang, Z. R., Ge, M., Pang, X. R., Song, P., & Wang, C. . (2023). The spatial distribution of interleukin-4 (IL-4) reference values in China based on a back propagation (BP) neural network. Geospatial Health, 18(2).

List of Cited By :

Crossref logo