Leukocyte Function In Patients Research Articles

Increased Spontaneous But Decreased Mitogen-stimulated Expression and Excretion of Interleukin 18 by Mononuclear Cells in Patients with Active Systemic Lupus Erythematosus

To measure serum concentration and analyze the expression of interleukin 18 (IL-18) mRNA in mononuclear cells of patients with systemic lupus erythematosus (SLE). IL-18 concentrations in sera and culture supernatants of peripheral blood mononuclear cells (PBMC) from healthy controls and patients with active SLE were measured by ELISA. PBMC and polymorphonuclear leukocytes (PMN) purified from patients with active SLE were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM), and lipopolysaccharide (LPS). Expression of IL-18 mRNA in cells was analyzed by RT-PCR. Serum IL-18 levels were significantly higher in SLE patients than in controls, and correlated with disease activity in SLE patients (r(2) = 0.602). Two patients receiving intravenous methylprednisolone therapy (1.0 g/day for 3 days) showed profound decreases in serum IL-18 levels after therapy. The quiescent PBMC from SLE patients (30/30) expressed IL-18 transcript more frequently than control PBMC (20/30). PBMC from SLE patients produced more IL-18 than control PBMC after 72 hours of incubation, by RT-PCR. PHA and PWM inhibited the production of IL-18 in PBMC from both SLE patients and controls. Inhibition by PWM was more pronounced than that by PHA, especially in SLE-PBMC. Control and SLE-PMN with or without LPS stimulation produced negligible IL-18. IL-18 is involved in the autoimmune derangement of leukocyte function in patients with active SLE.

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

15-Deoxyspergualin (DSG) is an alternative treatment modality for Wegener's granulomatosis (WG) patients refractory to conventional treatment. Nevertheless, it is unclear how DSG modulates disease activity in these patients. This study was conducted to investigate which parameters of adaptive and acquired immunity were influenced during two subsequent cycles of DSG treatment. Emphasis was put upon T cell and monocyte activation, neutrophil function and surface expression of proteinase-3 (PR-3). Anti-CD3/anti-CD28 and interleukin (IL)-15/IL-7-mediated T cell proliferation were assessed by fluorescence activated cell sorter (FACS) analysis using carboxyfluorescein succinimidyl ester (CSFE) labelling. Interferon (IFN)-gamma and IL-10 production were determined in the supernatants of these cultures by enzyme-linked immunosorbent assay. Monocyte activation was assessed in lipopolysaccharide (LPS)-stimulated whole blood, using tumour necrosis factor (TNF)-alpha as read-out. Neutrophil function was determined by measuring oxidative burst, chemotaxis and phagocytosis. T cell activation markers and PR3 expression were measured by FACS. All parameters were determined directly before and after each DSG cycle. Anti-CD3/anti-CD28-mediated T cell proliferation was reduced directly after DSG treatment. Directly before a subsequent cycle of DSG was started, T cell proliferation was increased. Similar findings were observed for IFN-gamma and IL-10 production by T cells. DSG did not influence IL-15/IL-7-mediated T cell proliferation. LPS-mediated TNF-alpha production was also impaired directly after DSG treatment. No influence on T cell activation markers, neutrophil function and surface PR-3 expression was observed in peripheral blood of these patients. Our data demonstrate that DSG influences T cell and monocyte activation in a reversible fashion. Although DSG causes neutropenia in these patients, it does not influence neutrophil function.

Impaired polymorphonuclear leucocyte function in patients undergoing hepatectomy: Adenylate energy charge and superoxide anion production in relation to hepatic mitochondrial redox state

Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polymorphonuclear leucocyte (PMN), focusing on energy charge and function, especially superoxide anion (O2-) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitable reduction of ferricytochrome c, the energy charge and O2- production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A, KBR greater than 0.7, n = 10; and group B, KBR less than 0.7, n = 8. The energy charge and O2- release in group B decreased significantly from preoperative values (P less than 0.001 and P less than 0.01 respectively) and when compared with group A (P less than 0.05 and P less than 0.01 respectively). These results suggest that impaired hepatic energy metabolism (KBR less than 0.7) in hepatectomized patients leads to impaired energy charge and O2- production in the PMNs.

Effect of Granulocyte-Monocyte Colony-Stimulating Factor Therapy on Leukocyte Function and Clearance of Serious Infection in Nonneutropenic Patients

Impaired leukocyte function in patients with serious infections may increase mortality. Granulocyte-monocyte colony-stimulating factor (GM-CSF) broadly activates peripheral monocytes and neutrophils. We performed a clinical trial of GM-CSF in septic, hemodynamically stable patients to see whether GM-CSF treatment improved leukocyte function and mortality. Randomized, unblinded, placebo-controlled, prospective study. A 600-bed academic tertiary care center with a 120-bed ICU census with a high proportion of immunocompromised, solid-organ transplant recipients. Forty adult patients with infections meeting the criteria for the systemic inflammatory response syndrome but without hemodynamic instability or shock. Patients with sepsis and a documented infection were randomized to a 72-h infusion of GM-CSF (125 microg/m2) or placebo. GM-CSF infusion caused the up-regulation of the beta2-integrin adhesion molecule CD11b and the appearance of the activated ("sticky" or "avid") form of the molecule on circulating neutrophils and monocytes. CD11b density and avidity increases in response to the administration of tumor necrosis factor-alpha were blunted prior to treatment in these patients with serious infection. GM-CSF partially repaired this blunted response on both monocytes and neutrophils. It also caused the down-regulation of the adhesion molecule L-selectin on neutrophils and the up-regulation of human leukocyte antigen on monocytes. These changes were consistent with a broad activation of the circulating leukocyte pool. Although mortality and organ failure scores were similar in both groups, infection resolved significantly more often in patients receiving GM-CSF. GM-CSF infusion up-regulated the functional markers of inflammation on circulating neutrophils and monocytes and was associated with both the clinical and microbiological resolution of infection. There was no detectable exacerbation of sepsis-related organ failure or other deleterious side effects with the administration of this proinflammatory agent to patients with serious infections.

Propofol and methohexital comparably affect polymorphonuclear leukocyte function in patients after cardiac surgery

Propofol and methohexital comparably affect polymorphonuclear leukocyte function in patients after cardiac surgery

The effects of allergen-specific immunotherapy on polymorphonuclear leukocyte functions in patients with seasonal allergic rhinitis

Immunotherapy plays an important role in the therapy of allergic rhinitis and bronchial asthma. However, there is not much information about the effects of allergen-specific immunotherapy (SIT) on the polymorphonuclear leukocyte functions. The aim of this study was to investigate the effects of specific immunotherapy on phagocytic and intracellular killing activities of polymorphonuclear leukocytes (PMN) derived from patients with seasonal allergic rhinitis. Twenty-four patients with seasonal allergic rhinitis documented to be sensitive to grass pollen were included in this study. Patients were divided into 3 groups. Group 1 ( n=7) received conventional immunotherapy whereas patients in Group 2 ( n=7) were treated with short-term immunotherapy and the third group ( n=10) were given placebo during the study process. Both phagocytic and intracellular killing activities were significantly increased ( p=0.002, p<0.0001, respectively) by conventional immunotherapy when compared to the first determination. In the short-term immunotherapy group, phagocytic activity was increased very significantly ( p=0.0001), whereas intracellular killing activity was not affected ( p=0.252). There were no changes in these parameters in the placebo group. These results suggest that allergen-specific immunotherapy has an enhancing effect on PMNs functions in the patients with seasonal allergic rhinitis. It should be clarified by further studies whether this enhancement might be considered as another beneficial effect of the immunotherapy.

Monocyte activation by circulating fibronectin fragments in HIV-1-infected patients.

To identify signals that can alter leukocyte function in patients receiving highly active antiretroviral therapy (HAART), we analyzed single blood samples from 74 HIV-1-infected patients and additional blood was collected at 90-day intervals from 51 HIV-1-infected patients over a 516 +/- 172 (mean +/- SD) day interval. Despite the absence of circulating immune complexes and normalization of phagocytic function, compared with controls, the fraction of patients' monocytes expressing CD49e and CD62L was decreased and expression of CD11b and CD86 increased. Plasma from 63% of patients but none from normal controls contained 110-120 kDa fibronectin fragments (FNf). Presence of FNf did not reflect poor adherence to therapy. Addition of FNf to normal donor blood in vitro replicated changes in monocyte CD49e, CD62L, CD11b, and CD86 seen in vivo. FNf also induced monocytes to release a serine proteinase, nominally identified as proteinase-3, that hydrolyzed cell surface CD49e. alpha(1)-Antitrypsin blocked FNf-induced shedding of CD49e in a dose-dependent manner. Plasma with a normal frequency of CD49e(+) monocytes contained antiproteases that partially blocked FNf-induced monocyte CD49e shedding, whereas plasma from patients with a low frequency of CD49e(+) monocytes did not block this effect of FNf. Electrophoretic analyses of plasma from the latter group of patients suggested that a significant fraction of their alpha(1)-antitrypsin was tied up in high molecular mass complexes. These results suggest that monocyte behavior in HIV-1-infected patients may be influenced by FNf and the ratio of protease and antiproteases in the cells' microenvironment.

Evaluation of polymorphonuclear leukocyte function in patients with lung cancer, using a chemiluminescence method

Evaluation of polymorphonuclear leukocyte function in patients with lung cancer, using a chemiluminescence method

Perioperative variation in phagocytic activity against Candida albicans measured by a flow-cytometric assay in cardiovascular-surgery patients.

Candidiasis is an opportunistic fungal infection that frequently occurs following modifications of host defenses. Major surgery can be responsible for such alterations, and therefore it increases the risk of fungal infection. The purpose of this study was to evaluate the perioperative impairment of leukocyte function in patients after cardiovascular surgery by measuring the phagocytic activity against Candida albicans by a flow-cytometric method. The average postsurgical decrease in phagocytosis in our patients was 11.4%. By univariate analysis, three factors, all related to antibiotic therapy, were significantly associated with an important decrease in phagocytosis; the use of antimicrobial therapy before surgery, the number of different antibiotics taken, and the length of antibiotic treatment. The results of our study showed that the use of antibiotics in patients undergoing cardiovascular surgery alters the normal phagocytic activity of the host immune system against C. albicans and that flow cytometry is a rapid and simple technique that helps in early identification of patients at high risk for Candida infections. The mechanisms by which surgery and antibiotics decrease phagocytosis remain to be elucidated.

Recombinant human interferon gamma therapy for osteopetrosis

A defect in leukocytic superoxide formation has been demonstrated in patients with congenital osteopetrosis. This leukocyte defect appears to be related to defective bone resorption. Because recombinant human interferon gamma therapy enhances superoxide production in patients with chronic granulomatous disease, we sought to determine whether a similar strategy could reverse the osteopetrotic condition. Interferon gamma, 1.5 micrograms/kg three times a week, was administered by subcutaneous injection for 6 months to eight patients with osteopetrosis. Urinary hydroxyproline and urinary calcium excretion increased markedly during therapy in parallel with a significant decrease in trabecular bone volume. Bone marrow scans demonstrated increased bone marrow production. The hemoglobin concentration, platelet count, and leukocyte production of superoxide increased significantly. No serious infections were encountered during the therapy. These data suggest that interferon gamma administration enhances bone resorption and leukocyte function in patients with osteopetrosis.

Effects of 1,25 dihydroxyvitamin D3 on leukocyte function in patients receiving chronic hemodialysis.

Effects of 1,25 dihydroxyvitamin D3 on leukocyte function in patients receiving chronic hemodialysis.

Studies of leukocyte functions in patients with periodontal diseases. 2. Chemotaxis of neutrophil and monocyte in patients with rapidly progressive periodontitis

重度進行性歯周炎 (RPP) 患者, および性, 年齢の一致した健常者それぞれ11名の末梢血より得た好中球および単球の走化性を, ボイテン・チャンバー法により調べた。その結果, RPP患者の好中球ランダム遊走能および走化性は, 健常者のそれと有意な差がなかったが, 至適濃度の走化性因子 (FMLP) に対する反応性は, RPP患者の方がより大きく分散した。単球の走化性および血清中の走化性活性も, RPP患者と健常者の問で差がなかった。また, FMLPによる好中球からのリソゾーム酵素放出性を, リゾチーム活性を測定することにより調べたが, RPP患者と健常者の間で差はなかった。以上の結果より, 食細胞が局所に遊走し, 脱顆粒して酵素を細胞外に放出するまでの過程では, RPP患者に顕著な機能欠損はないことが示唆された。

Effect of intralipid ® on some immunological parameters and leukocyte functions in patients with esophageal and gastric cancer

This study has been undertaken to investigate if the intravenous (i.v.) infusion of fat emulsions may be associated with impairment of some immunological functions thus increasing the risk of septic complications. Fifteen malnourished patients with advanced gastric or esophageal cancer received for 2 weeks preoperatively and 1 week after surgery an isocaloric and isonitrogenous TPN treatment with Intralipid ® (group A: n=8) or glucose alone (group B: n=7) as energy substrate. Cluster analysis of 11 nutritional parameters and some tests of the humoral and cellular immunity (IgG, IgM, C3c, Factor B; polymorphonuclear (PMN) cells, total lymphocytes, T and B lymphocyte counts; ‘in vitro’ PMN chemotaxis, adherence to nylon fibers, phagocytosis of latex particles) were sequentially determined. The incidence and severity of post-operative infections were investigated and a ‘sepsis score’ was calculated for each patient. Pre- and postoperative TPN were not associated with an improvement of the nutritional status. The humoral and cellular immune parameters showed the same behaviour in patients receiving Intralipid ® and in controls. The chemotactic activity of PMN cells was constantly normal, granulocyte adherence fluctuated below the normality range in controls, whereas phagocytosis of latex was similar in both groups. Post-operative infectious episodes were less severe in patients receiving Intralipid. ® Our results do not confirm that Intralipid ® adversely affects some aspects of the humoral and cellular immune response.

Polymorphonuclear and mononuclear leucocyte function in necrobiosis lipoidica and granuloma annulare.

Neutrophils and monocytes from patients with necrobiosis lipoidica (NL) and granuloma annulare (GA) were studied in vitro in order to detect functional abnormality. Phagocytosis of latex particles and zymosan-induced release of beta-glucuronidase were similar in patients and controls. Plasma from these patients did not enhance or inhibit phagocytosis or enzyme release from normal cells. Our studies suggest that peripheral blood leucocyte function in patients with GA and NL is normal, but this does not exclude a functional abnormality in the lesions.

Effect of high‐dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus

We have studied the effect of high-dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid-induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long-lasting abnormalities of PMN function in patients with lupus.

Leukocyte function in granuloma annulare.

Leukocytes from patients with granuloma annulare were studied in vitro in order to detect functional abnormalities. Random migration and chemotaxis of both polymorphonuclear leukocytes and monocytes were similar in patients and controls. Preincubation of normal cells with patients' plasma did not enhance or inhibit locomotion. Phagocytosis and oxidative burst as reflected by chemiluminescence were also normal. Peripheral blood lymphocytes incorporated uridine normally with and without stimulation by the non-specific mitogen phytohaemagglutinin. These studies suggest that peripheral blood leukocyte function in patients with granuloma annulare is normal, but do not exclude a functional abnormality in tissue.

Effect of prophylactic colchicine therapy on leukocyte function in patients with familial mediterranean fever

Patients with familial Mediterranean fever (FMF) who were part of a double-blind trial of daily colchicine as prophylaxis for their disease had leukocyte functions studied while receiving colchicine or placebo. Leukocytes taken from these patients while on prophylactic doses of colchicine produced normal quantities of leukocytic pyrogen, ingested bacteria normally, and migrated normally in chemotatic chambers. In addition these patients had normal numbers of circulating T and B lymphocytes as well as normal blastogenic reponses of their peripheral lymphocytes to mitogenic stimuli. The patients on colchicine, however, had significantly fewer neutrophils and monocytes accumulating at skin-window sites 24 hours after the initial abrasion. Because the early phase of the skin-window response was normal in these patients, the decreased late response may be related to a failure to amplify the initial inflammatory reaction. The reduced capacity to generate a normal inflammatory response may account for the failure of these patients to develop full attacks while taking colchicine.

Impaired leukocyte function in patients with poorly controlled diabetes.

In order to assess the influence of poor diabetes control on function of leukocytes, polymorphonuclear leukocytes (PMN's) from patients with poorly controlled but nonketotic disease were studied before and after therapy. Before treatment, phagocytosis was significantly reduced (p &amp;lt; .001) and, consequently, the rate of killing the test organism (type 25 pneumococcus) was decreased (p &amp;lt; .01). Following antidiabetes therapy phagocytosis improved significantly; while microbicidal rates also improved, they remained less than control values (p &amp;lt; .01). Serum from the untreated diabetics uniformly reduced phagocytosis and microbicidal rates of control granulocytes; serum from controls improved phagocytosis by the diabetic PMN's, but restored normal microbicidal rates in only half of the patients. This transferable inhibitory effect of hyperglycemic diabetic serum on control granulocytes was abolished by dilution, and was reproduced in normal serum by the isosmotic addition of glucose. These studies suggest that (1) PMN function may be impaired during periods of poor diabetes control, as has been shown previously in ketoacidosis, and (2) hyperglycemia or a closely related factor may contribute to the defect.

Leukocyte function in patients with leukemia.

Leukocyte function in patients with leukemia.

Leukocyte function in patients with leukemia

Leukocyte function in patients with leukemia