Cytokine concentrations are not predictive of bacteremia in febrile neutropenic patients

Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.     

Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa levels are significantly increased in acute myeloid leukemia patients

Serum interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R) and tumor necrosis factor-alfa (TNF-alpha) levels were determined in 66 previously untreated consecutive patients with acute myeloid leukemia (AML) and in 22 normal volunteers. The following mean (+/- SE) values were observed in patients and controls, respectively: 35 +/- 14.7 (range 0.5-500) and 0.7 +/- 0.02 (0.5-0.8 U/ml for IL-2 (p = 0.001); 1622 +/- 289 (110-10,600) and 422 +/- 30 (207-666) U/ml for sIL-2R (p = 0.0001); 1247 +/- 196 (218-4672) and 152 +/- 11 (75-308) pg/ml for TNF-alpha (p = 0.0001). With respect to the FAB classification system, we found a significantly different distribution of serum IL-2 mean values in distinct subcategories, i.e. 3.4 +/- 1.9 U/ml in M1-M2-M3 and 42.4 +/- 20.4 U/ml in M4-M5 subgroups, respectively (p = 0.01), whereas sIL-2R and TNF-alpha levels were 1144 +/- 322 U/ml and 1120 +/- 317 pg/ml in M1-M2-M3 patients and 1945 +/- 317 U/ml and 1270 +/- 259 pg/ml in the M4-M5 group. A significantly positive correlation between TNF-alpha and sIL-2R (r = 0.53; p = 0.002) was also detected in the M4-M5 group. Sixty-three out of 66 patients received an intensive chemotherapy program. Univariate analysis showed that age and sIL-2R greater than 2000 U/ml significantly affected both complete remission rate and overall survival, whereas by multivariate analysis, age was the only independent variable significantly influencing survival. These data confirm recent in vitro evidence suggesting the role of IL-2, sIL-2R, and TNF-alpha in the control of normal hematopoiesis and leukemogenesis. Since the availability of recombinant cytokines for clinical use in AML, it is crucial to understand their spectrum of interaction in order to select the appropriate combination for in vivo administration.     

Serum interleukin-1 beta levels correlate with neoplastic bulk in hairy cell leukemia

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and soluble IL-2 receptor (sIL-2R) serum levels were evaluated in 24 hairy cell leukemia (HCL) patients. Of these, three patients were studied at the time of diagnosis, 12 in relapse after interferon (IFN) therapy, eight with a partial response after IFN and one with a complete response after 2-deoxycoformycin (DCF) therapy. Statistically significant differences were observed in the serum levels of IL-1 beta and sIL-2R between HCL patients and controls. These were 400.3 pg per 0.1 ml (range 23.2-990) and 64.3 pg per 0.1 ml (20-115) for IL-1 beta and 4667.2 U/ml (488-7800) and 424.3 U/ml (188-666) for sIL-2R, respectively. In contrast, IL-1 alpha measurements showed no statistical differences between the two groups. A significant increase of sIL-2R (p = 0.01) and IL-1 beta (p = 0.03) serum levels was observed in patients studied at the time of diagnosis or in relapse compared to those in partial or complete remission. IL-1 beta serum levels directly correlated with sIL-2R (p less than 0.0001) and with hairy cell (HC) bone marrow infiltration, expressed by the HC index (p = 0.003). The comparison of IL-1 beta serum levels of HCL patients with those detected among 149 patients grouped according to diagnosis (Hodgkin's disease = 17, non-Hodgkin's lymphomas = 57, acute non-lymphoid leukemia = 46, and acute lymphoid leukemia = 29) indicate that HCL patients showed the highest IL-1 beta serum level increase, indicating that IL-1 beta could be used as a specific clinical marker of this disease.     

The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma

The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), which have angiogenic potential and interleukin-6 (IL-6), IL-1beta, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-beta) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-alpha, TGF-beta, IL-1beta did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology.     

大肠癌患者血清IAP、sIL-2R和IL-12变化

[目的]探讨检测血清IAP、sIL鄄2R和IL鄄12含量在大肠癌的辅助诊断、预后判断中的临床意义。[方法]采用单向免疫扩散法和ELISA法分别检测30例健康正常人及32例大肠癌患者手术前、后的血清IAP、sIL鄄2R和IL鄄12水平。[结果](1)大肠癌患者手术前血清IAP、sIL鄄2R水平均明显高于对照组(P<0.001和P<0.01),晚期组血清IAP、sIL鄄2R水平明显高于早期组(P<0.02和P<0.05),IAP与sIL鄄2R水平呈显著正相关(r=0.987,P<0.001);大肠癌患者血清IL鄄12水平明显低于对照组(P<0.05)。(2)串联IAP、sIL鄄2R两指标筛检大肠癌的敏感性为78.1%,特异性为93.33%,并联两指标筛检大肠癌,其敏感性为93.75%,特异性为73.3%。(3)手术后患者血清IAP、sIL鄄2R水平均明显低于手术前(P<0.001),早期组下降有明显差异性(P<0.001),而晚期组下降不明显(P>0.1);患者术后血清IL鄄12水平明显比术前升高(P<0.02),早期组上升显著(P<0.001),晚期组上升不明显(P>0.05)。[结论](1)检测患者血清IAP、sIL鄄2R水平对大肠癌的辅助诊断、病情判断、手术治疗和预后观察均有较高的临床价值。(2)联合检测血清IAP、sIL鄄2R对筛检大肠癌患者具有较高的敏感性。(3)血清IAP、sIL鄄2R和IL鄄12可作为指导大肠癌患者免疫学治疗较客观的指标。     

Serum levels of helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8), sIL-2R and beta 2-microglobulin in patients with B-CLL and benign B lymphocytosis.

Chronic B-lymphocytic leukemia (B-CLL) cells may be regulated by immune functions. In an attempt to analyze such functions, helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8) and sIL-2R and beta 2-microglobulin were measured in serum of patients at different stages of the disease. Patients were classified as having monoclonal lymphocytosis of undetermined significance (MLUS), stable or progressive B-CLL respectively. A significant, but modest, increase of IL-1 alpha was found in B-CLL as well as in MLUS patients whereas IL-6 levels were increased in MLUS only. sCD8 levels were increased both in MLUS and B-CLL but augmented sCD4 concentrations were found statistically significant only in progressive B-CLL. beta 2-microglobulin and sIL-2R were related to the extent of the monoclonal B-cell fraction. The data indicate an increased T-suppressor activity in both MLUS and B-CLL patients and a selective increase of helper T-cell activity in progressive B-CLL. A possible immunoregulatory influence of helper T cells on disease progression is discussed.     

Evaluation of inflammatory cytokines in malignant and benign pleural effusions

We measured the levels of inflammatory cytokines interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and serum in 65 consecutive patients: 32 with malignant pleural effusion (MPE) (group A), and 33 with inflammatory benign pleural effusion (BPE) (group B). Serum levels of 15 healthy individuals served as control. Concentrations of IL-1alpha were higher in serum compared to pleural fluid in both groups (47.1+/-33.9 vs. 25.9+/-1.7 fmol/ml, p<0.001, in group A; and 39.9+/-30.9 vs. 25.4+/-16.3 fmol/ml, p<0.02, in group B). Similarly, concentrations of IL-1beta and IL-2 were significantly higher in serum compared to pleural fluid in both groups. In contrast, IL-6, IL-8 and TNF-alpha were found at high concentration in MPE in comparison to serum IL-6: 171.8+/-60.4 vs. 7. 2+/-7 fmol/ml (p<0.001), IL-8: 1175.15+/-2385.6 vs. 285.2+/-187.2 pg/ml (p<0.05), TNF-alpha: 204.9+/-82.9 vs. 79.4+/-31.9 fmol/ml (p<0. 001). Similarly, pleural concentrations of IL-6, IL-8 and TNF-alpha were higher in BPE patients in comparison to serum IL-6: 124.3+/-56. 2 vs. 8.6+/-6.4 fmol/ml (p<0.001) IL-8: 2109.2+/-4121.5 vs. 291. 6+/-197.9 pg/ml (p<0.02), TNF-alpha: 183.8+/-28.2 vs. 86.2+/-23.9 fmol/ml (p<0.001). These data suggest that IL-6, IL-8 and TNF-alpha might be secreted locally at the site of active disease both in benign and malignant pleural effusions.     

Serum Levels of Interleukin-8 and Soluble Interleukin-6 Receptor in Patients with Stage-I Multiple Myeloma: A Case-Control Study

Objective: Multiple myeloma (MM) remains an incurable disease that needs better recognition and further research. Previous studies elucidated the interaction between myeloma cells and showed the necessity of bone marrow stromal cells for the initiation and progression of MM. Many chemokines and their receptors including interleukin-8 (IL-8) and soluble interleukin-6 receptor (sIL-6R) play important roles in this interaction. The main purpose of this study is evaluating the serum level of IL-8 and sIL-6R on stage-I of MM patients and healthy controls. Methods: Serum samples from 30 stage-I MM  patients (13 males and 17 females) and 30 healthy subjects as controls (13 males and 17 females) were examined in this study. The protein concentrations of serum IL-8 and sIL-6R were assessed by enzyme-linked immunosorbent assay (ELISA). Results: The mean level of IL-8 and sIL-6R were significantly elevated in stage-I MM. The mean levels of IL-8 were 1246.57±279.22 ng/ml in stage-I MM and 902.53± 294.61 ng/ml in controls (P<0.001). The mean levels of sIL-6R were 5.39±1.38 ng/ml and 4.1±1.14 ng/ml in stage-I MM and controls, respectively (P<0.001). The mean levels of IL-8 were 1342.18±193.4 ng/ml in patient females and 859± 278.2ng/ml in control females (P <0.001). The mean levels of sIL-6R were 5.21±1.55 ng/ml and 3.91±1.22 ng/ml in patient females and control females, respectively (P=0.01). The mean level of sIL-6R in patient males and control males were 5.63±1.43 ng/ml and 4.34±1.04 ng/ml, respectively (P=0.01). A significant correlation (Pearson’s correlation = 0.45, P=0.008) was observed in the population of females (patients and controls). Conclusion: The results of study suggest the possible involvement of IL-8 and the sIL-6R at stage-I MM and can better characterize the role of chemokines and their receptors in the disease process, especially in the early stages.     

Lack of correlation between defective cell-mediated-immunity and levels of secreted or circulating cytokines in a study of 90 cancer-patients

In this study we examined the levels of IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha and sIL-2R in the sera and culture supernatants of PHA-stimulated lymphocytes from a series of 90 cancer patients. The expression of the IL-2R p55 chain (alpha subunit) on PHA-stimulated lymphocytes was also evaluated together with the blastogenic response of peripheral blood mononuclear cells (PBMC) to PHA, PHA plus rIL-2 and rIL-2 alone. Ninety cancer patients (70 men and 20 women; mean age 57.8 years, range 27-80) with advanced solid malignancies at different sites were studied. The lymphocyte blastogenic response to PHA was significantly lower in cancer patients than in normal individuals. The proliferative response to rIL-2 alone was also significantly depressed in cancer patients. The frequency of CD25(+) PHA-stimulated lymphocytes from cancer patients was not significantly different from that of the control group. The serum values for IL-1 alpha, IL-1 beta, IL-6 and sIL-2R were significantly higher in cancer patients than in controls, while the serum level of IL-2 was within the normal range. The levels of sIL-2R released in the supernatant of PHA-stimulated PBMC of cancer patients were significantly lower than those of the control group. However, the levels of IL-1 alpha, IL-1 beta, IL-2, IL-6 and TNF-alpha, in the supernatants of PHA-stimulated PBMC of cancer patients were in the same range as those of the control group. These results suggest that the observed immune-deficiency in cancer patients cannot be explained on the basis of a defective production of key immunoregulatory cytokines since the lymphocytes from cancer patients produced physiological amounts of cytokines. We suggest that the observed defective cell-mediated immunity may be due to a defect in transmembrane signalling by the cytokines.     

肝细胞癌患者血清IL—6,IL—2系统的变化及相互关系

目的：研究肝细胞癌患者ＩＬ－６、ＩＬ－２、ｓＩＬ－２Ｒ的变化和意义。方法：分别采用ＡＢＳ－ＥＬＩＳＡ法、双抗体夹心ＥＬＩＳＡ法对４０例肝癌患者进行了ＩＬ－６、ＩＬ－２、ｓＩＬ－２Ｒ的测定,并与２６例肝地硬化和６６例健康献血员进行了对照。结果：肝细胞癌（ＨＣＣ）患者血清ＩＬ－６、ｓＩＬ－２Ｒ水平明显升高,而ＩＬ－２水平明显低于正常对照（ＮＣ）组（Ｐ〈０．０１）,ＨＣＣ组的ＩＬ－６水平高出正常１０倍以     

Interleukins, TNF-alpha and beta-2M in patients with B cell chronic lymphocytic leukemia

In order to investigate the possible existence of a prognostic factor for B cell chronic lymphocytic leukemia (B-CLL), we determined the serum levels of TNF-alpha, IL-1a, IL-1b, IL-2, sIL-2R, IL-6, IL-10 and beta-2M in 20 patients. We observed significant changes in sIL-2R and beta-2M levels, whereas in all stages of disease, TNF-alpha and other interleukins exhibited only mild changes. An excellent correlation between sIL-2R and beta-2M levels and disease activity wes reported. Patients with aggressive disease (Rai stages III and IV and Richter's syndrome) had increased levels. Patients who responded to therapy and with improved clinical status had decreased sIL-2R and beta-2M levels. However, patients with progressive disease and no response to therapy were associated with increased levels of sIL-2R and beta-2M. In conclusions, as serum levels of sIL-2R and beta-2M are increased in the aggressive stages of B-CLL, they may be used as reliable markers for monitoring B-CLL activity, showing response to treatment and early relapse and/or disease progression.     

急性髓系白血病患者化疗后血清IL-8、IL-6水平与感染的关系

目的：探讨急性髓系白血病(AML)患者化疗后粒细胞缺乏发热时血清白细胞介素8(IL-8)和白细胞介素6(IL-6)水平与感染的关系。方法：采用双抗体夹心酶联免疫吸附法(ELISA)检测42例AML患者和20名正常对照者血清IL-8、IL-6水平。结果：血清IL-8和IL-6水平在AML患者发热第1天均升高，其中病原学检查阳性组显著高于原因不明发热组(P均＜0.002)和仅有临床感染证据组(P均＜0.05)，仅有临床感染证据组也较原因不明发热组增高(P均＜0.02)，且革兰氏阴性菌感染者较革兰氏阳性菌感染者增高明显(P均＜0.01)；IL-8和IL-6呈显著正相关(r=0.841，P＜0.001)，并均与体温呈正相关(r=0.447和0.570，P＜0.005和P＜0.001)；并发败血症死亡患者的血清IL-8、IL-6水平呈持续增高。结论：应用夹心法ELISA联合检测血清IL-8、IL-6水平，将有助于确定AML患者化疗后粒细胞缺乏发热时的早期感染及其严重性。     

Aggressive non-Hodgkin's lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome

The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.     

A phase I trial combining carboplatin/doxorubicin with tocilizumab,an anti-IL-6R monoclonal antibody,and interferon-α2b in patients with recurrent epithelial ovarian cancer

BackgroundThe immune system is important in epithelial ovarian cancer (EOC). Interleukin-6 is associated with chemoresistance and an immune-suppressive tumor microenvironment. We investigated whether a combination of chemotherapeutics, blockade of interleukin 6 (IL-6) receptor (IL-6R; tocilizumab), and immune enhancer interferon-&agr; (Peg-Intron) is feasible, safe, and able to enhance immunity in patients with recurrent EOC.Patients and methodsIn this dose-escalation study, patients received tocilizumab 1, 2, 4, or 8 mg/kg i.v., q4 weeks during the first three cycles of carboplatin (AUC5) plus doxorubicin [pegylated liposomal doxorubicin (PLD) 30 mg/m² or doxorubicin 50 mg/m² i.v., day 1, q4 weeks, for six cycles]. At the highest tocilizumab dose (8 mg/kg), Peg-Intron (1 µg/kg s.c.) was added. Peripheral blood mononuclear cells were collected for immunomonitoring at baseline, after three and six cycles. Dose-limiting toxicity (DLT), CA-125, and radiologic response were evaluated.ResultsIn the 23 patients enrolled, no DLT was established. The most frequent grade 3/4 adverse events (CTCAE v4.03) were neutropenia (23%), febrile neutropenia (19%), and ileus (19%). No treatment-related deaths occurred. Using CT evaluation, 11 of 21 assessable patients responded, 6 had stable disease and 3 progressive disease. Patients receiving highest dose tocilizumab showed a functional blockade of IL-6R with increased levels of serum IL-6 (P = 0.02) and soluble IL-6R (P = 0.008). Consequently, immune cells displayed decreased levels of pSTAT3, myeloid cells produced more IL-12 and IL-1&bgr; while T cells were more activated and secreted higher amounts of effector cytokines interferon-γ and tumor necrosis factor-&agr;. An increase in sIL-6R was potentially associated with a survival benefit (P = 0.03).ConclusionsFunctional IL-6R blocking is feasible and safe in EOC patients treated with carboplatin/(pegylated liposomal)doxorubicin, using 8 mg/kg tocilizumab. This combination is recommended for phase II evaluation based on immune parameters.Clinical trial registerNCT01637532.     

Soluble immunological parameters and early prognosis of renal cell cancer patients

In local or metastatic cancer, a prognostic tumour marker could be a valuable tool in the selection of different treatments. In renal cell cancer (RCC) no such markers have been available. We therefore evaluated the association between several pretreatment serum markers, tumour classification and short term survival in RCC patients. Serum samples were collected before surgery and three months thereafter from 24 RCC patients. Interleukin-6 (IL-6), IL- 12, soluble IL-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (sICAM-1) were measured in serum samples using specific commercial enzyme immunoassay kits. Serum IL-6, sIL-2R and sICAM-1 levels before nephrectomy were significantly higher in non-local tumours than in local ones (mean IL-6 53 pg/ml versus 6.3 pg/ml, and sICAM-1 443 ng/ml versus 290 ng/ml, sIL-2R 3779 pg/ml versus 1796 pg/ml). In contrast, IL-12 levels were higher in local tumours (148 versus 102 pg/ml) and the levels increased significantly (P < 0.005) after removal of the primary tumour in patients with local disease. All patients with local tumours had normal IL-6 values, while only one with a non-local tumour had IL-6 levels below 10 pg/ml. In addition, IL-6 and sICAM-1 levels before operation were significantly higher in patients with short (less than one year) survival (p=0.007 to IL-6 and p=0.006 to sICAM-1). In contrast, patients with shorter survival had significantly lower IL-12 (p=0.03) levels. Our findings suggest that RCC induces changes in several immunological parameters. These soluble immunological factors, IL-6, IL-12, sIL-2R and sICAM-1, might have a role as prognostic factors in RCC.     

A review of the cytokine network in multiple myeloma: diagnostic,prognostic, and therapeutic implications

Because many studies have focused on growth factors in multiple myeloma, the study of the cytokine network appears to be useful for this purpose. Interleukin-6 (IL-6) and IL-2 with their soluble receptors (IL-3, IL-4, IL-10, and IL-11) have been examined. Plasma cells may produce IL-6 by an autocrine mechanism whereas a paracrine mechanism is believed to be involved in the production of IL-6 by bone marrow stromal cells through an interaction between adhesion molecules present on myeloma plasma cells and their respective receptors that are present on bone marrow stromal cells. In addition, control over production of IL-6 may be exerted by other ILs such as IL-1beta and IL-10. Among target cells, the growth of normal and myeloma plasma cells is supported by IL-6, which also induces the differentiation of myeloma plasmablastic cells into mature plasma cells. This last action also is shared by IL-3, IL-4, and, most likely, IL-8. Evaluation of the serum level of IL-6, C reactive protein, soluble IL-6 receptor (sIL-6R), and soluble IL-2 receptor (sIL-2R), together with the activity exerted by IL-3 and IL-4 on some cellular subsets, may constitute an additional element in the differential diagnosis of borderline cases. However, the concomitant evaluation of all immunologic parameters could be more useful than the value of a single IL. Serum levels of IL-6, sIL-6R, sIL-2R, and the expression of membrane-bound IL-2 receptors, both on bone marrow plasma cells and on peripheral blood mononuclear cells, are correlated with disease activity and disease stage. In addition, IL-6 and sIL-6R serum levels are believed to be correlated with the duration of disease-free survival because a high serum level at the time of diagnosis is believed to be correlated with a short duration of survival. However, some laboratory parameters may express the same prognostic value as high beta(2) microglobulin and lactate dehydrogenase (LDH) serum levels together with a high plasma cell labeling index are correlated with disease activity. Furthermore, if the evaluation is performed at the time of diagnosis, high values of these parameters are correlated with a short disease-free survival. A correlation between laboratory parameters and the serum level of several cytokines was demonstrated. Hence, the real advantage of the prognostic evaluation of cytokines is reserved for patients who do not exhibit uniform results with regard to beta(2) microglobulin and LDH serum levels, or, better, for borderline cases. With regard to the differential diagnosis, all immunologic parameters should be evaluated concomitantly rather than separately to confer a real prognostic value to results. Furthermore, a particular relation was found between a high sIL-6R serum level and a poor response to chemotherapy, therefore suggesting the possibility of identifying in advance a subset of patients with a high risk of treatment failure, as has already been demonstrated in other hematologic malignancies.Finally, the majority of studies indicate that interferons are used mainly in the immunotherapy for multiple myeloma, whereas many clinical trials should still be required for the evaluation of the effectiveness of anti-I-L6 antibodies or antiidiotypic vaccines in reference to the eligible patients for these particular therapies.     

A study of bacteremia in febrile neutropenic patients at a tertiary-care hospital with special reference to anaerobes

Patients with hematological malignancies who are receiving chemotherapy suffer prolonged periods of neutropenia, which leads to a greater risk of infection and mortality. A prospective study was conduced to determine the incidence of bacteremia in patients of hematological malignancies over a 2-yr period. A total of 119 episodes of febrile neutropenia occurred among 96 consecutive patients, of which 35 episodes were associated with bacteremia. Forty-four percent of the isolated bacteria were Gram-positive aerobes and 46% were Gram-negative aerobes. Staphylococcus aureus, Enterococcus spp., and Escherichia coli were the most common isolates. Gram-negative bacteremia was associated with a higher mortality. Anaerobes accounted for 4.4% of all isolates. The episodes of anaerobic bacteremia were polymicrobial and had a fatal outcome. A high incidence of antimicrobial resistance among aerobic and anaerobic bacteria was also recorded. Compared to previous years, a shift from a predominating Gram-negative to a Gram-positive etiology was noted. The initial empiric antibiotic regimens should be based on a local knowledge of the most common causative microorganisms, their sensitivity pattern, and the outcome of bacteremia.     

Monocyte disorders associated with T cell defects in patients with solid tumors.

T cells proliferate in response to autologous monocytes in the autologous mixed lymphocyte reaction (AMLR). AMLR was found to be impaired in patients with advanced cancer (stages III and IV), whereas normal values were found in the early stages of the disease (stages I and II). Peripheral T lymphocytes from patients with advanced stages also exhibited a decreased ability to produce Interleukin-2 (IL-2) during an AMLR response, whereas production of IL-2 by T cells in stages I and II was comparable to that of normal donors. The impaired IL-2 production by T lymphocytes in the AMLR was associated with high concentrations of soluble interleukin-2 receptor (sIL-2R) in culture supernatants and reduced expression of membrane-bound interleukin-2 receptors (IL-2R) on the same AMLR-activated T lymphocytes. These abnormalities in T cells from cancer patients were demonstrated to be associated with dysfunctions of autologous monocytes. Thus monocytes from patients with advanced cancer exhibited diminished expression of HLA-DR antigens and produced low levels of Interleukin-1 beta (IL-1 beta) and Tumor Necrosis Factor a (TNFa). No changes were detected in the expression of HLA-A, -B, -C antigens. The results presented here demonstrate that decreased in vitro T cell responses may be attributed to monocyte dysfunctions in these patients and provide new information for a better understanding of the impaired T cell function in cancer patients.