Change And Clinical Significance Of Cytokine Pattern For Hemophagocytic Lymphohistiocytosis In Children

Background:Hemophagocytic lymphohistiocytosis in children is a rapid-develop-ing disease which early symptoms are atypical、diagnosis is extremely difficult, and many patients died of unproper diagnosis and treatment of it. Along with the deepen understanding of the disease, case reports in children are growing,but the pathological physiological mechanism of it still not clear, immune disturbance maybe one of the major reasons. Case reports that hyperproduction of cytokines was an important presentation of immune disturbance in HLH.Objective:To investigate the change of cytokines in children with hemophagocytic lymphohistiocytosis and analyze the diagnostic and prognostic significance of them.Methods The levels of serum IL-18、 IL-10、IL-12、TNF-α、NF-κβ and neopterin in16patients who were diagnosed and treated in Zhengzhou Children’s Hospital during January2011and May2012and ten healthy volunteers were determined by enzyme linked immuno sorbent assay. The patients were divided into two groups by prognosis:remission group and death group.According to different process of chemotherapy, the remission group was divided into HLH1-6groups,the death group was divided into HLHa-d groups. According to the Critical Illness Scores of the children, the dead children were divided into aHLH1-5groups,the remission children were divided into bHLH1-5groups. Patients’prognosis follow-ups were carried out via phone calls.Results:1、The levels of serum IL-10and neopterin in16HLH children were signi-ficant higher than healthy control, and the difference had obvious statistical meaning (P<0.01),IL-18、IL-12、NF-κβ and TNF-a were higher than the healthy control, and the difference had statistical meaning (P<0.05).In16HLH children,IL-10had dis-tinctly positive correlateions with NF-κβ (r=0.747P<0.01),had positive correlate- ions with neopterin (r=0.567P<0.05), IL-18had distinctly positive correlations with TNF-α(r=0.686P<0.01),had positive correlations with IL-12(r=0.542P<0.05)2, The levels of IL-18、IL-10、IL-12、NF-κβ、TNF-a and neopterin in the remission group declined with chemotherapy, the difference between HLH1group and another HLH groups were statistically significant(P<0.05).In the death group, the levels of NF-κβ、IL-12and neopterin had no downward trend with chemotherapy, the difference between HLHa group and another HLH groups were not statistically significant (P>0.05). The level of TNF-a declined with chemotherapy,but the downward trend was not obvious,the difference between the HLHa group and the HLHb group、the HLHb group and the HLHc group had no statistically meaning(P>0.05). The level of IL-10decline sharply in the first one week of chemotherapy, the difference between the HLHa group and the HLHb group was obvious statistically significant (P<0.01). The level of IL-18declined in the first two weeks of chemotherapy, the difference between the HLHa group and the HLHb group、the HLHa group and the HLHc group had no statistically meaning (P<0.05).3、The levels of serum IL-12and neopterin in aHLH1group were higher than these in bHLH1group, the difference between two groups had statistically meaning(P<0.05). The level of serum NF-κβ in aHLH2group was evidently higher than it in the bHLH2group,the difference between them had significant statistical significance(P<0.01).The levels of serum IL-10and IL-12in aHLH2group were higher than these in bHLH2group, the difference between two groups had statistically meaning(P<0.05).The levels of serum NF-κβ、TNF-α、neopterin and IL-10in aHLH3group were evidently higher than these in bHLH3group, the difference between them had significant statistical significance(P<0.01), the levels of serum IL-18and IL-12in aHLH3group were higher than these in bHLH3group, and the difference between them had the statistically meaning(P<0.05). The levels of serum TNF-α and neopterin in aHLH4group were evidently higher than these in bHLH4group, and the difference between them had significant statistical significance(P<0.01), the levels of serum IL-18、IL-10and IL-12in aHLH4group were higher than these in bHLH4group, and the difference between two groups had statistically meaning(P<0.05).The levels of serum NF-κβ、TNF-α、 neopterin、IL-12and IL-10in aHLH5group were evidently higher than these in bHLH5group, the difference between them had significant statistical significance (P<0.01)Conclusions:1、The significant increase of IL-10and neopterin with moderate increase of IL-18、IL-12、TNF-α and NF-κβ is a specific cytokine pattern for children with HLH.2、In the remission group, the levels of serum IL-18、IL-10、IL-12、NF-κβ、TNF-a and neopterin declined with chemotherapy. In the death group, the downward trend was not obvious. Preliminary confirmed that the prognosis of HLH patients was related to the trend of cytokines during chemotherapy.3、The levels of scrum IL-18、IL-10、IL-12、TNF-α、NF-κβ and neopterin in the death group were higher than these in the remission group.Preliminary confirmed that cytokines in HLH patients were connected with severity of the disease.