Serum Interferon-gamma Inducible Protein 10 Research Articles

Profile and clinical significance of interferon gamma-inducible protein-10 (IP-10) and its receptor in patients with hepatocellular carcinoma.

Chemokines play a vital role in tumor progression, metastasis and prognosis; however, the profile and clinical significance of gamma interferon-inducible protein-10 (IP-10) and its receptor (CXCR3) in patients with hepatocellular carcinoma (HCC) have not been well evaluated. Liquid-phase chip technology was used to detect the serum IP-10 in 85 patients with HBV-related HCC, 50 patients with chronic hepatitis B (CHB) and 50 liver cirrhosis subjects (CS); simultaneously, the CXCR3 and Alpha fetoprotein (AFP) were determined. Additionally, their mRNA or protein expression levels in peripheral blood mononuclear cells (PBMC), liver tumor and paracancerous tissues were quantified using qRT-PCR or ELISA. Moreover, the IP-10 and CXCR3 expression was verified by the online data from Gene Expression Omnibus. Furthermore, the relationships of serum IP-10, CXCR3 and AFP levels with their overall survival rate were also analyzed. The levels of IP-10 and CXCR3 in HCC group were significantly higher than those in CHB and CS groups, and their mRNA of PBMC is significantly positive correlation with those in their liver tissues or HBV DNA load (P < 0.0001), respectively. The serum IP-10 and CXCR3 in HCC were significantly correlated with tumor differentiation, metastases staging and distant metastasis (P < 0.05), but not related to gender, age and tumor size (P > 0.05, except IP-10 based on age). The serum IP-10 (142.6 pg/mL) and CXCR3 (241.2 pg/mL) could be differential diagnostic surrogates that distinguish HCC from CS, and the lower IP-10 level may be conducive to the postoperative survival of HCC patients. Moreover, the IP-10 and CXCR3 would be related to anti-tumor immunity in HCC patients and be a potential target for treatment of HCC.

Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients.

Background & aimsSerum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients.MethodsIn serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS.ResultsIn 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases.ConclusionsA strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.

Pretreatment serum levels of interferon-gamma-inducible protein-10 are associated with virologic response to telaprevir-based therapy

AimTelaprevir (TVR) remarkably improves the efficacy of interferon treatment for chronic hepatitis C. Interleukin-28B (IL28B) genotype and interferon-gamma-inducible protein-10 (IP-10) level predict virologic response to peg-interferon (Peg-IFN)/ribavirin (RBV) therapy. We aimed to investigate the usefulness of pretreatment serum IP-10 levels and IL28B genotyping in predicting sustained virologic response (SVR) to TVR-based triple therapy. MethodsIn this multi-center study, patients infected with hepatitis C virus genotype 1 with high viral load (⩾5.0logIU/mL) were treated with TVR for 12weeks and Peg-IFN/RBV for 24weeks in Japan. IL28B genotype, serum IP-10 levels, other clinical parameters, and drug dosages were assessed before treatment. ResultsWe included 121 patients who were treated with TVR for at least 8weeks and Peg-IFN/RBV for 24weeks. The median IP-10 levels were significantly lower in rapid virologic response (RVR) or SVR in the IL28B non-TT genotype group, with no significant difference in the TT genotype group. RVR rates were significantly lower in the group with higher serum IP-10 levels (>450pg/mL). In the non-TT IL28B genotype group, RVR and SVR rates were significantly lower in the group with higher IP-10 levels. SVR rates in the group with lower IP-10 levels (<450pg/mL) increased to 82% for those showing RVR, but reduced to 27% in the group with higher IP-10 levels for those not showing RVR. ConclusionsDetermination of serum IP-10 levels before treatment could be useful for predicting favorable virologic response to TVR-based triple therapy, especially in patients with IL28B non-TT genotype.

Serum levels of leptin and IP-10 in preeclampsia compared to controls.

Preeclampsia (PE) is a pregnancy-specific syndrome with a complex, yet elusive, etiology. The production of a variety of factors probably implicated in diverse pathways may trigger endothelial dysfunction leading to PE pathogenesis. The aim of the present study was to investigate and compare the concentrations of leptin and interferon-gamma-inducible protein-10 (IP-10), factors characterized by inflammatory, immunomodulatory and angiogenic activities, and to evaluate their possible interaction in women with normotensive pregnancy and PE. The study was carried out on a total of 58 pregnant women, 29 women with PE and 29 controls. Serum leptin and IP-10 levels were determined by enzyme-linked immunosorbent assay. Serum leptin levels were significantly increased in women with PE compared to controls and this difference was stronger in women with severe PE (p < 0.001). Although IP-10 serum concentrations were elevated in our preeclamptic women, this difference was not statistically significant. No correlation was found between leptin and IP-10. The results of the present study support a significant role of leptin in PE; however, this association was independent from serum IP-10 levels, suggesting that there is no crucial interplay between these two proteins in PE.

Association ofInterferon-Gamma Inducible Protein 10Polymorphism with Treatment Response to Pegylated Interferon in HBeAg-Positive Chronic Hepatitis B

Interferon-gamma inducible protein 10 (IP-10) plays an important role in the clinical outcome of chronic hepatitis B (CHB). This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) G-201A of the IP-10 gene and treatment response to pegylated interferon (PEG-IFN) in patients with hepatitis B e antigen (HBeAg)-positive CHB. We retrospectively analysed data of patients with HBeAg-positive CHB treated with PEG-IFN for 48 weeks. Virological response (VR) was defined as HBeAg clearance and HBV DNA <2,000 IU/ml at 24 weeks post-treatment. The SNPs G-201A, IFNL3 (rs12979860) and HLA-DPA1 (rs3077) were assessed. Among 107 patients, VR was achieved in 45 (42.1%) patients. Hepatitis B surface antigen (HBsAg) clearance and decline (<100 IU/ml) were observed in 10 (9.3%) and 22 (20.6%) patients, respectively. The distribution of GG, GA and AA genotypes of G-201A was 76.6%, 19.6% and 3.7%, respectively. Patients with GG genotype, compared to those with non-GG genotype, achieved higher VR rate (48.8% versus 19.2%; P=0.011), decreased HBsAg (25.6% versus 4.0%; P=0.019), and demonstrated a trend in HBsAg clearance (11.0% versus 4%; P=0.294). Patients with GG genotype had more rapid HBsAg decline and higher baseline serum IP-10 levels than those with non-GG genotype (432.2 ±339.0 versus 257.3 ±145.7 pg/ml; P=0.028). SNPs rs12979860 and rs3077 were not associated with VR. Logistic regression analysis suggested that SNP G-201A was an independent predictor of VR (odds ratio 3.81, 95% CI 1.31, 11.12; P=0.014). Data from this study demonstrated for the first time that IP-10 polymorphism is independently associated with treatment response to PEG-IFN in patients with HBeAg-positive CHB.

Serum Fractalkine and Interferon-Gamma Inducible Protein-10 Concentrations Are Early Detection Markers for Acute Renal Allograft Rejection

ObjectiveThe aims of this study were to determine if characterization of serum concentrations of interferon-gamma inducible protein-10 (IP-10), fractalkine, and their receptors (CXCR3 and CX3CR1) were predictive of acute allograft rejection in kidney transplant recipients. MethodsKidney transplant recipients (n = 52) were enrolled in this study and divide into either the acute rejection (AR, n = 15) or non–acute rejection (NAR, n = 35) groups. Serum samples from recipients were collected 1 day prior to transplantation and on days 1, 3, 5, 7, and 9 post-transplantation. The accuracy of chemokine concentrations for predicting acute rejection episodes was evaluated using receiver operator characteristic (ROC) curves. ResultsAR was diagnosed in 15 patients based on histologic changes to renal biopsies. AR patients had significantly higher serum fractalkine, CXCR1, IP-10, and CXCR3 levels compared to levels observed in the NAR group and healthy controls. Fractalkine and IP-10 had the largest area under the ROC curve at 0.86 (95% confidence interval: 0.77–0.96). Following steroid therapy, chemokine levels decreased, which may serve to predict the therapeutic response to steroid therapy. ConclusionMeasuring serum levels of fractalkine, IP-10, and their receptors (especially the fractalkine/IP-10 combination) may serve as a noninvasive approach for the early diagnosis of renal allograft rejection.

Su1003 High Pre-Treatment Serum Interferon-Gamma-Inducible Protein 10 (IP-10) Levels Is Associated With HBsAg Seroconversion After Peginterferon Therapy in HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B

Introduction: Serum levels of interferon-gamma inducible protein 10 (IP-10) are a marker for immune activity and may be associated with an increased probability of HBeAg loss after pegylated interferon (PegIFN) therapy. The aim of this study is to compare the chronological change of serum IP-10 levels in chronic hepatitis B patients with and without HBsAg seroconversion after PegIFN therapy. Materials and Methods: Sixty chronic hepatitis B patients (HBeAg positive (n=30) and HBeAg negative (n=30)) were recruited and treated with PegIFN for 48 weeks. Demographic and clinical data of the patients were recorded. Serum IP-10 was measured at baseline, on-treatment weeks 12, 24 and 48 and week 72 post-treatment. Results: Forty-four males and 16 female chronic hepatitis B patients were included. The median age of patients was 34 years, and 7 of 60 patients achieved HBsAg seroconversion at week 96 post-treatment. Baseline characteristics including age, sex, ALT, HBV DNA level and HBsAg level were not statistical different between the two groups (Table 1). The mean level of serum IP-10 at baseline was 751±588 and 250±293 pg/ml in patients with and without HBsAg seroconversion, respectively. At baseline and week 48, IP-10 level were significantly higher in patients with HBsAg seroconversion than patient without HBsAg seroconversion (Table 2). A cut off value of baseline serum IP-10 level of less than 200 pg/ ml predicted no one achieving HBsAg seroconversion at week 96 post-treatment (100%, 32/32). Whereas, up to 25% (7/28) of CHB patients with a baseline serum IP-10 level more than 200 pg/ml achieved HBsAg seroconversion at week 96 after PegIFN therapy. The odds ratio for HBsAg seroconversion at week 96 after PegIFN therapy was 1.37 for every 100 pg/ml positive increment of baseline IP-10 (OR 1.37; 95% CI, 1.07-1.59; P<0.01). The dynamic change of the post-PegIFN treatment serum IP-10 level was significantly different among two groups of patients. In the HBsAg seroconversion group, the serum IP-10 level which was not statistically significant changed during treatment, however, the IP-10 was significantly decreased in week 72 post-treatment. On the other hand, the IP-10 level tended to significantly increase during the treatment period in chronic HBV patients without seroconversion after Peg-IFN treatment (Figure 1). Conclusions: Pre-treatment serum IP-10 was higher in patients who achieved HBsAg seroconversion at week 96 after peginterferon therapy. This pilot study showed that a cut off value of 200 pg/ml serum IP-10 level predicted the outcome of treatment with Peg-IFN in chronic hepatitis B patients. Table 1. Comparison of demographic, baseline ALT, HBV DNA and HBsAg level between patients with and without HBsAg seroconversion at week 96.

Higher frequency of peripheral CD3CXCR3 and CD4CXCR3 positive blood cells in HCV patients in context of bile acid retention

Background: Chronic hepatitis C infection is worldwide a leading cause of end stage liver disease. High levels of serum interferon-gamma-inducible protein-10 (IP-10) are associated to inferior antiviral therapy response. In a cohort of 300 HCV patients we recently showed an association between higher IP-10 serum levels, cholestasis and higher DPPIV serum activity. DPPIV was described as cleavage enzyme of serum IP-10 (Casrouge et al., JCI 2011) which induces an antagonist form of IP-10.

Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype

Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity. 60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maximal increase from baseline during that time (ΔTmax) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs - CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped. Temperatures rose by 1.2±0.8°C, peaking after 12.5h. ΔTmax was strongly associated with 1st phase virological decline (r=0.59, p<0.0001) and was independent of gender, cirrhosis, viral genotype or baseline HCV-RNA. The association with 1st phase decline was seen in patients with rs12979860CC genotype (r = 0.65, p <0.0001) but not in CT/TT (r = 0.13, p = 0.53) and patients with CC genotype had a higher DTmax (1.4 ± 0.8 C vs. 0.8 ± 0.6 +C, p = 0.001). DTmax was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12979860CC [corrected].ΔTmax weakly predicted early virological response (AUC=0.68, CI 0.49-0.88). Temperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness.

Predictors of Chronic Hepatitis C Evolution in HIV Co-Infected Patients From Romania

BackgroundDue to a recent alarming increase in the number of HIV-HCV co-infected patients in Romania.ObjectivesA cross sectional study was conducted to assess the baseline predictors of liver disease evolution.Patients and Methods83 HIV-HCV co-infected patients, untreated for HCV infection, were evaluated for viral replication, liver fibrosis (estimated by a noninvasive marker - FIB4), and plasma levels of IP-10 (interferon-gamma inducible protein 10) - a cytokine associated with an unfavorable outcome of HCV infection.ResultsThe median value for HCV viral load was high (6.3 log10 IU/mL), 98.8% of the patients were infected with HCV genotype 1. Although 53% of the patients received antiretroviral therapy (cART), only 31.8% of these achieved undetectable HIV levels. HCV viral load was significantly higher in patients with AIDS (6.4 vs. 6.1 log10IU/mL; P = 0.04), and in those naïve for cART (6.5 vs. 5.9 log10 IU/mL; P = 0.04). Severe fibrosis was directly correlated with immunosupression (56% vs. 17.4%, P = 0.03), HCV replication (6.1 vs. 4.9 log10IU/mL P = 0.008), and IP-10 median values (312 vs. 139 pg/ml, P=0.008). A serum IP-10 level higher than 400 pg/mL was significantly associated with FIB-4 median values (4.09 vs. 1.7, P = 0.004), HCV viral load (6.4 vs. 6.1 log10 IU/mL, P = 0.02) and ALT level (206.8 vs. 112.4 IU/L, P = 0.05).ConclusionsAn important part of the HIV-HCV co-infected patients had negative baseline predictors for the evolution of HCV infection; their therapeutical management must be conducted with special attention towards adherence and potential overlapping drug toxicities. High concentrations of plasma IP-10 are reliable markers for the severity of liver disease.

IL28B and interferon‐gamma inducible protein 10 for prediction of rapid virologic response and sustained virologic response in HIV‐HCV‐coinfected patients

A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV-infected patients. The predictive value of interferon-gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV-HCV-coinfected patients are not available. Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV-HCV-coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin. A total of 72 HIV-HCV-coinfected patients were included in the study; 68% had HCV genotype (GT)-1/4 and 32% had HCV GT-2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non-C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT-1/4 and GT-2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non-C/C patients with high IP10. The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV-HCV coinfection.

Ribavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling

The therapeutic mechanisms of ribavirin for hepatitis C are unclear. Microarray analyses have shown that ribavirin increases induction of interferon-stimulated genes. We evaluated viral kinetics, serum cytokine expression, and viral mutagenesis during early stages of peginterferon therapy with and without ribavirin. Fifty patients with chronic hepatitis C virus (HCV) infection genotype 1 were randomly assigned to groups that were given peginterferon alpha-2a, with or without ribavirin, for 4 weeks; all patients then received an additional 44 weeks of combination therapy. First- and second-phase viral kinetics were evaluated. Serum levels of interferon-gamma-inducible protein-10 (IP10), monokine induced by interferon-gamma, and monocyte chemoattractant protein 1 were quantified as measures of the interferon-stimulated genes response. NS5A and NS5B were partially sequenced, and mutation rates were calculated. The first-phase decrease in HCV RNA was similar between groups. Patients who received ribavirin had a more rapid second-phase decrease, compared with patients who did not receive ribavirin-particularly those with an adequate first-phase decrease (0.61 vs 0.35 log10 IU/mL/week; P = .018). At 12 hours, fold induction of serum IP10 was higher in patients given the combination therapy than those given peginterferon only (7.6- vs 3.8-fold; P = .01); however, the difference was greatest in patients with an adequate first-phase decrease in HCV RNA. IP10-induction correlated with first- and second-phase kinetics and with ribavirin serum concentrations on day 3. HCV mutation rates were similar between groups. Ribavirin improves the kinetics of the early response to therapy in patients with an adequate initial response to peginterferon. Induction of interferon-stimulated cytokines correlates with viral kinetics following ribavirin therapy, suggesting that ribavirin promotes interferon signaling.

The production of interferon-γ-inducible protein 10 by granulocytes and monocytes is associated with ulcerative colitis disease activity

To clarify which types of cells produce interferon-gamma-inducible protein 10 (IP-10) and whether IP-10 is associated with the development of ulcerative colitis (UC), we investigated IP-10 production in UC patients. Serum IP-10 levels were measured using enzyme-linked immunosorbent assay in 29 patients with active and 21 with inactive UC and in 20 controls. The production of IP-10 by granulocytes and monocytes adsorbed to G-1 beads was examined. In 21 active UC patients treated with granulocyte and monocyte/macrophage adsorptive apheresis (GMA), serum IP-10 levels were measured before and after treatment. IP-10-positive cells in UC mucosa were also examined immunohistochemically using tissues obtained by surgical resection and colonoscopic biopsies. Serum IP-10 levels in active UC patients were significantly higher than those in inactive patients, although even in the latter the levels were increased compared with those in controls. IP-10 production by granulocytes and monocytes in active UC patients was significantly higher than that in controls. Furthermore, the number of IP-10-positive cells was elevated in the colonic mucosa of patients with active UC, and one of the main subpopulations of IP-10-positive cells was granulocytes. Serum IP-10 levels decreased following GMA treatment in responders, but not in nonresponders. Interestingly, serum IP-10 levels before GMA were higher in responders than in nonresponders. In parallel with the serum levels, IP-10-positive cells also decreased following GMA treatment. Serum IP-10 levels reflected UC disease activity, and the source of IP-10 was granulocytes and monocytes. Furthermore, serum IP-10 levels may be a marker for the responsiveness of patients to GMA treatment.

Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size

Objectives: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). Design and methods: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. Results: Patients with AMI showed significantly higher serum IP-10 levels (137.5 ± 79.8 pg/mL) than control subjects (91.2 ± 40.1 pg/mL) and patients with AP (93.3 ± 41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. Conclusions: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.

Helper T-lymphocyte-related chemokines in healthy newborns.

Atopic disease is characterized by an imbalance in cytokines secreted from Th1 and Th2 lymphocytes. The association between atopy and serum levels of atopy-related chemokines in umbilical cord blood (UCB) has not been evaluated. This study formulates the reference ranges of thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin (EOX), monocyte chemotactic protein 1 (MCP-1), and interferon-gamma-inducible protein 10 (IP-10) in UCB of term neonates and investigates the relation between these chemokines and the development of atopy during infancy. The concentrations of total IgE and chemokines in UCB serum were measured by microparticle immunoassay and sandwich enzyme immunoassay, respectively. A total of 124 singleton healthy newborns were investigated. Fifty-three (43%) infants had family history of allergic diseases, and 26 (21%) had increased serum total IgE concentrations. The median (interquartile range) serum TARC, MDC, EOX, MCP-1, and IP-10 concentrations, in pg/mL, were 425 (300-639), 786 (561-1050), 36 (28-45), 156 (116-205), and 38 (29-49), respectively. Multiparity was associated with increased serum MDC (p = 0.017). Serum chemokine concentrations were not associated with total IgE levels or family history of allergies. The median (interquartile range) serum MDC concentrations in newborns who developed wheezing during infancy and those without wheezing were 1259 pg/mL (945-1523) and 782 pg/mL (551-992), respectively (p = 0.010). This study provides reference ranges of Th-specific chemokines in UCB serum of singleton term neonates. Increased serum MDC concentrations at birth are associated with the occurrence of wheezing during infancy.

Increased serum levels of interferon-gamma-inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis.

We measured serum interferon-gamma-inducible protein 10 (IP-10) and monokine induced by gamma interferon (MIG) levels to investigate the role of these molecules in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). Serum IP-10 and MIG levels were significantly increased in patients with active HLH compared with those of healthy controls. Serum MIG levels decreased gradually during the course of disease in a patient who recovered without therapy. On the other hand, rapid reduction of MIG and IP-10 levels was observed after chemotherapy in a patient with severe HLH. IP-10 and MIG mRNA expression was enhanced in liver and spleen, and IP-10 mRNA expression was enhanced in bone marrow in the patients, suggesting activated macrophages that infiltrated in these organs as one of the main producers of these cytokines. Serum IP-10 and MIG levels showed a significant correlation with serum IFN-gamma levels. In addition, these chemokines had a significant correlation with fever and serum LDH levels, which are clinical indicators of disease activity of HLH. These results suggest that IP-10 and MIG which are produced by activated macrophages by the stimulation of IFN-gamma, play an important role in the pathophysiology of HLH, by recruitment of activated Th1 cells into the tissues or organs.