Depressed Natural Killer Cell Activity in Schizophrenic Patients

Factors that suppress natural killer (NK) cell activity were examined in a random sample of 73 schizophrenic patients. NK activity in these patients were compared with 25 healthy age, sex and race matched controls. The mean percent of NK activity was 21% in the schizophrenic group compared with 30% percent in the controls. The difference between these two groups was statistically significant. The mean percent of NK activity in the chronic undifferentiated schizophrenic subgroup and schizoaffective subgroup were 20% and 22% respectively. The degree of suppression of NK activity in the chronic undifferentiated subgroup was higher than in the schizoaffective one, but the difference was not statistically significant. The two subgroups were comparable regarding other immune related variables such as total white cell count, neutrophils, lymphocytes, total protein, albumin, globulin, immunoglobulins and stress. The lower impairment of NK activity in the schizoaffective subgroup may be due to their exposure to lithium which can enhance immune functions. Factors associated with significant suppression of NK activity in schizophrenic patients were physical restraint, number of psychotropic medications, number of chronic non-psychiatric diagnoses and race. Psychosocial stressors were associated with suppression of NK activity but it was not statistically significant. Our results identify factors associated with reduced NK activity observed in certain schizophrenic patients and NK activity in these patients may be the result of interaction between various factors.     

Natural Killer Cell Activity Test Helps to Suspect Aggressive Natural Killer Cell Leukemia - Diagnostic Challenge

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an aggressive clinical course. We aimed to assess the clinicopathological characteristics of the difficult to diagnose ANKL. During ten years, nine patients with ANKL were diagnosed. All the patients exhibited aggressive clinical course and underwent the BM study to rule out lymphoma and hemophagocytic lymphohistiocytosis (HLH). BM examination showed varying degrees of infiltration of neoplastic cells, which were mainly positive for CD2, CD56, cytoplasmic CD3 and EBV in situ hybridization. Five BM aspirates showed histiocytic proliferation with active heomphagocytosis. Normal or increased NK cell activity test results were obtained from 3 patients who were available for testing. Four had multiple BM studies until diagnosis. An aggressive clinical course and positive EBV in situ hybridization, often with associated secondary HLH, should raise the suspicion of an ANKL. Conducting additional supplementary tests such as NK cell activity and NK cell proportion would be helpful for the diagnosis of ANKL.     

Altered Natural Killer Cell Activity in Childhood Acute Non-lymphoid Leukaemia

Peripheral blood and bone marrow mononuclear cells from 25 children with acute non-lymphoid leukaemia were analysed for natural killer cell activity and for cells with the Leu-7 and Leu-11b (CD 16) markers. Significantly reduced spontaneous cytotoxicity was detected in peripheral blood from children with untreated and active acute non-lymphoid leukaemia compared with that of the controls (P = 0.01 and P less than 0.05). Patients in remission, however, had normal natural cytotoxicity and normal numbers of Leu-7 and Leu-11b (CD 16)-positive cells. The natural killer cell activity in bone marrow from patients with untreated acute non-lymphoid leukaemia was also significantly reduced (P = 0.025). On the other hand, patients in remission had both an increased percentage of Leu-7 and Leu-11b (CD 16)-positive cells (P less than 0.05) and an increased natural killer cell activity (P less than 0.0005) in their bone marrow cells in comparison with the control group. This augmented natural killer cell activity is most probably a result of anti-leukaemic treatment. Stimulation with recombinant alpha interferon and recombinant interleukin 2 caused an increase in natural killer cell activity that was both significant and normal in both peripheral blood and bone marrow from children with acute non-lymphoid leukaemia.     

Reduced Natural Killer Cell Activity in Multi-Drug Resistant Pulmonary Tuberculosis

Cellular immune status in five patients with multi-drug resistant pulmonary tuberculosis was investigated and compared with five matched controls with non-resistant tuberculosis. A significant reduction in fresh natural killer (NK)-cell activity was found in the resistant group ( P < 0.005). There were no significant differences between the two groups in lymphocyte phenotype, proliferation or PPD-specific cytotoxicity. Reduced NK-cell function may play a role in the pathogenesis of multi-drug resistant pulmonary tuberculosis.     

Inhibition of Natural Killer Cell Activity by Antigen-Antibody Complexes

The natural killer (NK) cell activity of human peripheral blood mononuclear cells was found to be inhibited by precipitated tetanus toxoid anti-tetanus toxoid complexes (Te/aTe) as well as soluble Te/aTe. Preincubation of the immune complexes with protein A decreased the inhibition of NK cell activity. When mononuclear cells were preincubated with interferon (IF) or interleukin 2 (Il-2) before incubation with Te/aTe, the immune complex-induced inhibition was decreased, while IF or Il-2 added after incubation with the immune complexes had no effect. Using NK cell-enriched suspensions in a single cell agarose assay, the immune complexes were shown to inhibit NK cell activity by inhibiting the formation of effector/target cell conjugates.     

Pidotimod Stimulates Natural Killer Cell Activity and Inhibits Thymocyte Cell Death

Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca⁺⁺ionophore-induced apoptosis.     

Reduced Natural Killer Cell Activity and Okt4/Okt8 Ratio in Epileptic Patients

A number of immune abnormalities have been found in epileptic patients. Several, but not all, of these defects appear to be related to the toxic effects of antiseizure medications. To study the basis of immune abnormalities in epilepsy, various populations and subsets of peripheral blood mononuclear cells (PBMC) from epileptic patients were enumerated and their functions examined. Reduced natural killer cell activity was found in the patients and their siblings. Enumeration of the PBMC showed a lower proportions of Leu 11+ cells in some of the patients which may account for the lower natural killer activity. A reduced ratio of OKT4+/OKT8+ cells was also found in the patients. Responses of patient PBMC to the T-cell mitogens phytohemagglutinin, concanavalin A and the B-cell mitogen pokeweed mitogen were unchanged as were the total number of rosette-forming cells in the patients. The results provide more evidence for a genetic basis for some of the immune abnormalities in epileptic patients.     

The Role of Calmodulin in Human Natural Killer Cell Activity

Calcium is known to play an essential role in the lytic mechanism of natural killer cells (NK), which form a subset of large granular lymphocytes. Many of the intracellular effects of calcium are mediated through the calcium-binding protein calmodulin. In this study we have demonstrated that the specific calmodulin inhibitors (naphthalene-sulphonamides) inhibit NK activity in humans at IC50's of 6.9 microM for W7 and 5.2 microM for W13. Comparison of the potency of these compounds with their less active counterparts suggests that NK activity is calmodulin-dependent.     

Natural Killer Cell Activity in Multiple Sclerosis and Myasthenia Gravis

Because of the potential role of Natural Killer (NK) cells in viral immunity and immunoregulation, we have undertaken a study of NK activity of peripheral blood lymphocytes from both Multiple Sclerosis (MS) and Myasthenia Gravis (MG) patients, two chronic diseases in which a viral etiology and an induced autoregulatory abnormality are strongly implicated. No significant difference between the mean NK activity in MS patients and controls was observed. A difference was observed between the NK activity of female MG patients and female controls, but no difference was seen between male MG patients and controls.     

Pidotimod Stimulates Natural Killer Cell Activity and Inhibits Thymocyte Cell Death

Abstract

Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca⁺⁺ionophore-induced apoptosis.     

Enhancement of Natural Killer Cell Activity by Nocardia opaca Fractions

Three molecules derived from Nocardia opaca bacteria, NDCM, NWSMP, and PG, have been shown to express immunomodulating properties. The present study was aimed at assessing the effects of these derivatives on natural killer (NK) activity. Two experimental protocols were adopted, consisting of incubating whole or Percoll fractionated NK cells in vitro with those substances, and the other in which the derivatives were administered in vivo to mice and the activity assessed later. Incubation of spleen cells in vitro with NWSMP or its precursor NDCM promoted NK activity. This effect could be observed after only 2 h of incubation and continued until day 2. Percoll fractions 1-3, which contain most of the NK activity, were enhanced to a similar extent. Band 4, which is usually devoid of such activity, remained unresponsive even after contact with the N. opaca derivatives. PG was practically ineffective upon all the subsets. The results of experiments in vivo correlated with those obtained in vitro in that NWSMP and NDCM, but not PG, promoted NK activity. Bands 1-3 were similarly enhanced, the effect was observed after short treatment times, and could be partially cancelled by the concomitant administration of anti-interferon antibodies (anti-IFN Ab). All these findings suggest that the promoting effects of N. opaca derivatives are mediated through alpha/beta IFN. In contrast to the results observed on spleen NK cells, NK cells from the peritoneum displayed susceptibility mainly to PG, and much less to NWSMP or NDCM. The administration of PG to mice in vivo had a particularly marked promoting effect upon the cytotoxic activity of peritoneal cells. One logical explanation for the difference observed between PG and NWSMP or NDCM may be related to the specific IFN inducing properties of these compounds as well as to the different responsiveness of the NK cells present in the spleen and peritoneal cavity.     

Effect of Helixor A on Natural Killer Cell Activity in Endometriosis

Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosisMaterials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker.Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV.Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.     

Chemotherapeutic Agents and Modulation of Natural Killer Cell Activity in Vitro

This study investigated the effect of various clinically used chemotherapeutic agents on non-modulated and human alpha Interferon (IFN) modulated natural killer cell (NK) activity. The inhibitors of DNA synthesis, Adriamycin, Cis-Platinum, 5-Fluorouracil and Methotrexate, did not alter NK cell activity at coaparable clinically used doses, Similarly, Vincristine and Vinblartlne, which are antimi totic agants, did not affect the NK activity. Only inhibitors of RNA synthesis L-Aaparaginase and Actinomycin D reduced non-modulated and IFN modulated NK cell activity.     

Modulation of Natural Killer Cell Activity in Peripheral Blood by Physical Exercise

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.     

Glutaurinb Enhances the Depressed NK Cell Activity of Tumor Patients

The effect of glutaurine, a newly discovered parathyroid substance, on human NK cell activity and on lymphocyte markers was studied. Both in vivo and in vitro treatment with glutaurine markedly enhanced the depressed natural lymphocytotoxicity of tumor patients without influencing their lymphocyte subpopulations. On the other hand it had no effect on the NK cell activity of healthy lymphocytes and of tumor patients' lymphocytes with originally “normal1” NK activity. The NK-enhancing effect of glutaurine could not be explained by augmentation of the number of potential effector cells. It is suggested that glutaurine increases the originally low spontaneous killer activity of tumor patients' lymphocytes through an indirect regulatory mechanism.     

Suppression by Human Placental Protein 14 of Natural Killer Cell Activity

ABSTRACT: Human decidua of early pregnancy contains considerable numbers of CD3^? CD56⁺ natural killer (NK) cells. In this study, two major protein products of the decidua, placental protein 14 (PP14) and placental protein 12 (PP12), were tested for the ability to regulate human NK cell activity. In vitro overnight exposure to PP14 of blood lymphocytes or purified large granular lymphocytes (LGL) resulted in suppression of cytotoxicity against K562 target cells in a 4-h ⁵¹Cr release assay. The NK inhibition was dependent on concentrations of PP14, being detectable at 5 μg/ml and reaching maximum at 50 μg/ml. Manifestation of PP14-induced NK suppression required 18-h contact with NK cells. The suppression of NK activity by PP14 was not abolished by indomethacin. In a target binding assay the number of PP14-treated LGL binding to K562 was comparable to that of untreated ones. By contrast with PP14, PP12 produced no effects on NK cells. These results indicate that PP14 suppresses the function of NK cells, which might be involved in prevention of maternal immune rejection of fetus at the fetomaternal interface.     

The Effects of Stress on Natural Killer Cell Activity in Healthy Men1

Several studies have shown that exposure to acute laboratory stressors produces an immediate change in immune function. We examined the effects of a mild laboratory stressor on natural killer (NK) cell cytotoxicity and on psychological and cardiovascular measures in 24 adult males. Subjects in the experimental condition worked on the Stroop task without interference for 30 min with blood samples drawn at baseline, 10, 20, and 30 min into the task, and 40 min after completing the task. The 30-min stressor produced increases in self-reported stress and tension, and in SBP, DBP, and HR. It was also associated with a decrease in NK cell cytotoxicity 40 min after the stressor. Results are discussed in relation to the effects of mild and intense stressors and future research implications.     

Modulation of Natural Killer Cell Activity in the Rheumatoid Joint and Peripheral Blood

Natural killer (NK) cell activity and its regulation in synovial fluid (SF). synovial tissue (ST). and peripheral blood (PB) was studied in 23 patients with active rheumatoid arthritis (RA). NK activity was reduced in PB (P< 0.005), SF (P <0.002), and ST of patients with RA compared to the PB of 28 healthy controls. NK activity in SF was inversely correlated wilh disease activity as measured by erythrocyte sedimentation rate (r=-0.561; P<0.02). Poly I:C. an Interferon inducer, stimulated NK activity in RA patients' PB and SF and control subjects' PB to similar extents. However, augmentation of NK activity by interleukin-2 was significantly greater in SF than in PB of RA (P<0.02). Preincubation of mononucleur cells with indomethacin significantly increased the NK activity of normal and RA PB but had no effect on that of SF. These observations suggest that the NK activity may be reduced in both PB and SF of RA and (hat functional differences between populations of cells with NK-like activity and/or differences in the control or modulation of NK activity exist between PB and SF.     

Modulation of Mouse Natural Killer Cell Activity by the Serum Thymic Factor

After mice had been treated with serum thymic factor (FTS). we observed an increase or a decrease in the NK activity, depending on the duration of treatment and mouse strain: an increase for C57BL/6, BALB/c, A, and nu/nu and a decrease for NZB and CBA mice. The fact that treatment of C57BL/6 mice with FTS produces the same effect as thymeciomy—that is, an increase -on the NK activity and returns the augmented NK activity of thymeclomized mice to normal levels suggests that FTS has multiple effects with different results depending on the level of differentiation of the target cells. Different mechanisms of action of FTS on NK cells are discussed.