The Value Of Cytokine Profiling In Identifying Fever Caused By Infection And Tumor In Children With Lymphoma

Introduction:Fever is a common clinical symptom in patients with lymphoma,which is usually caused by tumor complicated with infection or the tumor itself.The causes of fever in lymphoma are closely related to cytokine.Understanding the changes of cytokine in these conditions may have implications for the etiology of fever in patients with lymphoma,which not only can improve the prognosis of patients,but also can avoid the abuse of antibiotics in children with lymphoma.Objectives:The aim of this study were to determine the serum cytokine levels in children and to analyze the roles played by cytokine profiles in identifying fever caused by tumor complicated with infection or the tumor itself.Methods:Six cytokine levels including IL-2,IL-4,IL-6,IL-10,TNF-? and IFN-? from 134 pediatric patients treated in the Department of Children's Hospital of Zhejiang University School of Medicine from January 1,2011 to December 31,2016 were determined by cytometric bead array(CBA)technology.In the above cases,97 patients were diagnosed with lymphoma.The other 37 cases were adenoid hypertrophy without fever.In patients with infectious fever and tumor fever,we also determined hsCRP(High-sensitivity C-reactive protein)and PCT(Procalcitonin).Results:The hsCRP,PCT in lymphoma patients had no statistical difference between infectious fever group and tumor fever group(P>0.05).The median levels of IL-10 and IFN-y in tumor fever group(16.7 and 87.25pg/mL,n=6)were significantly higher than those in infectious fever group(6.1 and 7.05pg/mL,n=62),the fever group caused by bacterial infection(6.35 and 7.95pg/mL,n=14)and the fever group caused by fungal infection groups(6.5 and lO.Opg/mL,n=10)(P<0.05).The median level of IFN-y in tumor fever group(87.25pg/mL,n=6)was significantly higher than those in the fever group caused by viral infection(6.3pg/mL,n=5)(P<0.05).The median ratios of IL-6/IL-10 and IL-6/IFN-y in tumor fever group(1.02 and 0.35,n=6)were significantly lower than those in infectious fever group(9.03 and 6.03,n=62),the fever group caused by bacterial infection(4.76 and 4.23,n=14)and the fever group caused by fungal infection groups(10.39 and 5.32,n=10)(P<0.05).The median ratio of IL-6/IFN-y in tumor fever group(0.35,n=6)was significantly lower than those in the fever group caused by viral infection(1.59,n=5)(P<0.05).The cytokine had no statistical difference between the lymphoma patients without infection(no fever)(n=24)and the control group(n=37)(P>0.05).The median level of IL-10 in Hodgkin lymphoma(6.5pg/mL,n=4)was significantly higher than those in no-Hodgkin lymphoma(3.0pg/mL,n=20)in patients without infection and fever(P<0.05).The cytokine had no statistical difference between B cell lymphoma(n=16)and T cell/NK cell lymphoma(n=4)in patients without infection and fever(P>0.05).The median levels of IL-6,IL-10 and TNF-a in post-treatment of infectious patients without fever(12.55,5.3 and 2.1pg/mL,n=8)were significantly lower than those in pre-therapy of infectious patients with fever(216.4.6.5 and 3.55pg/mL,n=8)(P<0.05).There was no statistical difference between the above six cytokine levels at the time of pre-and post-treatment of tumor fever group(P>0.05),however,a statistical difference trend of the median IL-10 levels between the two groups was found.Conclusions:Elevated IL-10 and IFN-? levels,reduced ratios of IL-6/IL-10 and IL-6/IFN-?in children with lymphoma can indicate tumor fever.This may help to identify the fever caused by tumor complicated with infection and the tumor itself in patients with lymphoma.