scholarly journals Defective natural immunity: an early manifestation of human immunodeficiency virus infection.

1995 ◽  
Vol 182 (3) ◽  
pp. 789-799 ◽  
Author(s):  
H Ullum ◽  
P C Gøtzsche ◽  
J Victor ◽  
E Dickmeiss ◽  
P Skinhøj ◽  
...  
Keyword(s):  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Lak Cells ◽  
Natural Immunity ◽  
Cd4 Cells ◽  
Nk Cell Activity ◽  
Ifn Alpha ◽  
Lak Cell ◽  
Lak Cell Activity

Cytotoxicity mediated by natural killer (NK) and lymphokine-activated killer (LAK) cells may be of significance in host defense against viral infections. This study included 347 patients infected with human immunodeficiency syndrome virus (HIV) type 1 and 110 controls. The NK cell activity, either unstimulated or stimulated with interferon-alpha (IFN-alpha) or interleukin-2 (IL-2), and the LAK cell activity were suppressed in patients, but the NK/LAK cell activity did not differ between patients with AIDS and patients without AIDS. However, the IFN-alpha-stimulated NK cell activity and LAK cell activity were reduced in patients with symptoms of HIV disease (CDCIV) when compared with asymptomatic patients (CDCII+III). When the data were analyzed by multiple linear regression, the percentage of CD4+ cells had a positive effect on these two parameters in patients without AIDS, whereas the percentage of CD4+ cells had no significant effect on unstimulated and IL-2-stimulated NK cell activity in these patients. In controls and AIDS patients, the percentage of CD4+ cells had no effect on NK/LAK cell activity in multiple linear models. The total number of CD16+ cells was low in patients compared to controls, whereas the percentages of CD16+, CD56+, and CD16+CD56+ were either normal or elevated. Therefore, the decrease in NK cell subpopulations did not contribute to the observed depression in NK/LAK cell activity in vitro. It is concluded that natural immunity is suppressed in HIV-seropositive patients primarily because of a qualitative defect of the NK/LAK cells. This qualitative defect includes a reduced responsiveness to IFN-alpha, which is progressive until the onset of symptoms, and possibly related to the loss of CD4+ cells.

Renal cell carcinoma: treatment with recombinant interleukin-2 plus beta-interferon.

1990 ◽  
Vol 8 (3) ◽  
pp. 460-467 ◽  
Author(s):  
R L Krigel ◽  
K A Padavic-Shaller ◽  
A R Rudolph ◽  
M Konrad ◽  
E C Bradley ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Local Recurrence ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Nk Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Beta Interferon

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-beta) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-beta was administered three times weekly by intravenous (IV) bolus injection with 5 x 10(6) Cetus U/m2 of IL-2 and 6 x 10(6) U/m2 of IFN-beta to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Early Diagnosis and Treatment of the Patients with Acquired Hemophagocytic Lymphohistiocytosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3552-3552
Author(s):  
Zhao Wang ◽  
Yini Wang ◽  
Cuicui Feng ◽  
Liping Tian
Keyword(s):  
Early Diagnosis ◽  
Diagnostic Criteria ◽  
Peripheral Blood ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Nk Cell ◽  
Clinical Symptoms ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Final Diagnosis ◽  
Nk Cell Activity

Abstract Acquired hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition characterized by uncontroling hyperinflammation on the basis of various infection, tumor and inherited immune deficiency. Awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time. In this study, we reviewed 57 suspected HLH patients from March 2006 to June 2008. 25 healthy subjects were enrolled in the study as control. NK cell activity in peripheral blood was tested by a released LDH assay. Meanwhile, solution interleukin-2 receptor (sCD25) was examined with ELISA double antibody sandwich assay. The level of glycosylated ferritin was also detected and the ratio of glycosylated ferritin to ferritin was determined. 41 out of 57 patients were definitely diagnosed according to HLH-2004 diagnostic criteria in this study and 16 patients were excluded. We found that the level of NK cell activity and the ratio of glycosylated ferritin in the all 41 final diagnozed HLH patients were significantly lower than those in the 16 excluded patients and 25 healthy control subjects (p<0.01). Meanwhile, the level of sCD25 in peripheral blood was much higher in all the 41 HLH patients than that in the excluded and healthy people (p<0.05). We compared the coincidence of each diagnostic index in the 41 HLH patients before and after final diagnosis. It was found that 100% patients had abnormal expression on NK cell activity, sCD25 and glycosylated ferritin in the early disease. The three diagnostic indexes were more sensitive and specific than other indexes, such as fever, hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypo-fibrinogenemia. 41 diagnosed patients received the regimen containing methylprednisolone and immunoglobulin, with or without fludarabine, 26 out of 41 were markedly improved after treatment, 10 out of 41 were exacerbated, and other 5 patients gave up treatment. It is concluded that detection of NK cell activity, sCD25 and glycosylated ferritin may play a very important role in the early diagnosis of HLH. Our data also suggest that fludarabine combined with methylprednisolone and immunoglobulin (FDIg) may provide a new viewpoint for HLH therapy.

Experimental study on interleukin 6 activity against tumor; Regulation of interleukin-2 induced lak cell activity

1993 ◽  
Vol 5 (4) ◽  
pp. 263-267
Author(s):  
Lisheng Lu ◽  
Zhengyan Cui ◽  
Ling Zhang ◽  
Denghua Li ◽  
Zhigang Tian
Keyword(s):  
Experimental Study ◽  
Interleukin 6 ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Lak Cell ◽  
Lak Cell Activity

Cordyceps sinensis as an Immunomodulatory Agent

1996 ◽  
Vol 24 (02) ◽  
pp. 111-125 ◽  
Author(s):  
Yuh-Chi Kuo ◽  
Wei-Jem Tsai ◽  
Ming-Shi Shiao ◽  
Chieh-Fu Chen ◽  
Ching-Yuang Lin
Keyword(s):  
Tumor Necrosis ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Cordyceps Sinensis ◽  
Fruiting Bodies ◽  
Nk Cell Activity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the Iymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) production on human mono-nuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 =; 71.0 ± 3.0 and 21.7 ± 2.0 μg/ml, respectively), NK cell activity (IC50 =; 25.0 ± 2.5 and 12.9 ± 5.8 μg/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 =; 9.6 ± 2.3 and 5.5 ± 1.6 μg/ml, respectively). TNF-α production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 =; 2.7 ± 1.0 and 12.5 ± 3.8 μg/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.

Comparison of Immunological and Endocrinological Markers Associated with Major Depression

2003 ◽  
Vol 31 (1) ◽  
pp. 36-41 ◽  
Author(s):  
H Jozuka ◽  
E Jozuka ◽  
S Takeuchi ◽  
O Nishikaze
Keyword(s):  
Major Depression ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Depression Scale ◽  
Serum Cortisol ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Nk Cell Activity ◽  
Self Rating

Natural-killer-(NK)-cell activity and blood levels of interleukin 2 (IL-2), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEA-S) and cortisol were measured in 17 patients with major depression and 10 control subjects. Depression severity was evaluated using the Zung Self-rating Depression Scale. NK-cell activity and IL-2 levels were measured using a chromium-51 release test and an enzyme-linked immunosorbent assay, respectively. Radioimmunoassays were used to measure serum cortisol, DHEA and DHEA-S. As would be expected, patients with major depression had a higher score on the Zung Self-rating Depression Scale than healthy controls. Compared with controls, NK-cell activity and levels of cortisol and DHEA were reduced in patients with major depression, whereas IL-2 levels were increased. No difference was observed in DHEA-S levels between patients and controls. A reduction in NK-cell activity and DHEA levels, and an increase in IL-2 levels appear to be associated with major depression. Whether these changes are the cause or the consequence of the depression remains to be determined.

Influence of in vivo hypobaric hypoxia on function of lymphocytes, neutrocytes, natural killer cells, and cytokines

1993 ◽  
Vol 74 (3) ◽  
pp. 1100-1106 ◽  
Author(s):  
M. Klokker ◽  
A. Kharazmi ◽  
H. Galbo ◽  
I. Bygbjerg ◽  
B. K. Pedersen
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Cd8 Cells ◽  
The Absolute

We have investigated the effects of short-term hypoxia in vivo on the human cellular immune system. Seven young healthy volunteers were placed in a decompression chamber (380 Torr) for 20 min with or without supplemental O2. The leukocyte concentration increased during hypobaric conditions because of an increased concentration of lymphocytes. The absolute and relative concentration of CD16+ natural killer (NK) cells increased markedly during hypoxia and returned to pretest values after 2 h of recovery. The NK cell activity of blood mononuclear cells (BMNC, %lysis/fixed no. of BMNC) boosted with interferon-alpha, interleukin-2 (IL-2), and indomethacin rose in parallel with unboosted NK cell activity during hypoxia. The percentage of CD4+ and CD8+ cells declined during hypoxia, whereas the absolute concentration of both CD8+ cells and CD14+ monocytes increased. Although the BMNC composition varied, the proliferative responses of BMNC after stimulation with phytohemagglutinin, purified derivative of tuberculin, and IL-2 did not change significantly. The in vitro production of interleukin-1 beta and IL-2 in supernatants obtained after stimulation of BMNC with phytohemagglutinin or lipopolysaccharide was not affected. The chemiluminescence response of neutrocytes increased 2 h after hypoxia. It was concluded that acute hypoxia induced marked alterations in the immune system and that the NK cells are especially sensitive to the hypoxic stimulus.

scholarly journals Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1355-1360 ◽  
Author(s):  
F Santiago-Schwarz ◽  
C Panagiotopoulos ◽  
A Sawitsky ◽  
KR Rai
Keyword(s):  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Lymphocytic Leukemia ◽  
Lak Cell ◽  
Cell Chronic Lymphocytic Leukemia

Abstract We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B- CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B- cell growth and/or growth stimulation of the leukemic clone in B-CLL.

scholarly journals Impaired natural killer cell recycling in childhood chronic neutropenia with morphological abnormalities and defective chemotaxis of neutrophils

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 99-105
Author(s):  
A Komiyama ◽  
H Kawai ◽  
S Yamada ◽  
K Aoyama ◽  
M Yamazaki ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Activity ◽  
Normal Lymphocyte ◽  
Nk Cell Activity ◽  
51Cr Release ◽  
Ifn Alpha ◽  
Effector Target ◽  
Chronic Neutropenia

Natural killer (NK) cell activity was measured by a 51Cr-release assay using K562 target cells in 12 neutropenic children. NK cell activity was depressed in four patients who had childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The percentage of lysis at a 40:1 effector-target ratio was 28.4% to 42.1% (P less than .001) of the normal lymphocyte value during the study period (32 to 40 months). NK cell activity was normal in the other eight children with chronic neutropenia without any of these neutrophil abnormalities: lazy leukocyte syndrome, Shwachman syndrome, or dysgammaglobulinemia type I with neutrophil defects. NK cell activity of the four patients was depressed at 5:1 to 40:1 effector-target ratios. The NK cells responded to in vitro interferon (IFN)-alpha and interleukin 2, as did normal lymphocytes, but the activated levels were still lower than those of normal lymphocytes (P less than .01). Because NK cells kill a target through recognition, binding, killing, and detaching, and they repeat this lytic sequence (ie, recycling), the localization of the NK cell defect was further analyzed in the four patients using both 51Cr- release and single cell-in-agarose assays. The patients' NK cells were normal in recognizing, binding, and killing a target but were defective in recycling; the estimated maximum recycling capacity (MRC) values in a four-hour assay were 1.8 to 2.4 (P less than .01), as compared with the normal lymphocyte value of 5.5 +/- 0.6 (mean +/- SD). The stimulation of the effector cells with 1,000 U/mL IFN-alpha did not significantly increase the estimated MRC. These results demonstrate that NK cells are defective in recycling in some type of childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The NK cell deficiency is of clinical interest in terms of its relationship to the recurrent infections, development of malignancy, and dysgranulopoiesis in the disorder.

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