Proliferation Of Peripheral Mononuclear Cells Research Articles

Inhibitory effects of human umbilical cord-derived mesenchymal stem cells on proliferation of peripheral blood mononuclear cells from spondyloarthritis patients

To explore the inhibitory effects of human umbilical cord-derived mesenchymal stem cells (hUCMSC) on the proliferation of peripheral blood mononuclear cells (PBMC) from spondyloarthritis (SpA) patients. A total of 12 SpA patients at Chinese PLA General Hospital were recruited from May 2012 to October 2012. Information on demographic characteristics, disease and functional activity was collected. Isolated PBMC were stimulated by phytohemagglutinin (PHA, 1 µg/ml) in the presence or absence of hUCMSC.The proliferation of hUCMSC was suppressed by irradiation with Co60 (30 Gy) before co-culturing with PBMC. The proliferation of PBMC was determined by Cell Counting Kit-8 (CCK-8). Cell cycle profiles of PBMC were analyzed by flow cytometry. The association of inhibitory effect of hUCMSC with the disease and functional activity of SpA patients was examined. After coculturing with hUCMSC by cell-to-cell contact for 5 days, the proliferation of PBMC stimulated by PHA (1 µg/ml) was significantly inhibited by hUCMSC in a dose-dependent manner.The inhibition rate of the proliferation of PBMC cocultured with hUCMSC by cell-to-cell contact was higher than that by Transwell culture (57% ± 17% vs 32% ± 12%, P < 0.01). Compared to PBMC cultured alone, a larger number of PBMC cocultured with hUCMSC were in phase G1 (86% ± 3% vs 68% ± 5%, P < 0.01) while a lower number of cells in phases S and G2 (8% ± 3% vs 26% ± 5%, P < 0.01). No association was found between the inhibitory effect of hUCMSC and the disease and functional activity. The proliferation of PBMC from SpA patients may be inhibited by hUCMSC. And hUCMSC have therapeutic potentials for SpA patients.

Successful treatment of congenital pulmonary alveolar proteinosis with intravenous immunoglobulin G administration

The authors report a female patient with congenital pulmonary alveolar proteinosis (PAP). She had two brothers who died from the same disease. BAL did not improve her progressive respiratory failure. After intravenous immunoglobulin G (IVIG) administration for complicated hypogammaglobulinemia, she recovered from respiratory failure. The efficacy of IVIG was confirmed by recovery from deterioration in respiratory status and improvement in chest CT findings on two separate occasions. Subsequently, the patient remains free from respiratory symptoms for more than 3 years on an ongoing regimen of monthly IVIG. She had no surfactant protein (SP) B deficiency. Alveolar macrophages (AM) obtained from her BAL fluid were small and showed decreased phagocytotic activity. Immunostaining revealed weak expression of PU.1 in her AM, a key protein in AM maturation. All nucleotide sequences of granulocyte-macrophage colony stimulating factor (GM-CSF), GM-CSF-receptor and PU.1 were normal. Endotoxin-induced GM-CSF release from peripheral mononuclear cells (PMNC), and proliferation of PMNC in response to GM-CSF were normal. In addition, an antibody against GM-CSF, as seen in adult patients with idiopathic PAP, was not detected in the serum or BAL fluid. Although the patient's PMNC secreted only small amounts of IgG and IgM, an EB virus-derived cell line of her B cells secreted IgM as much as normal control cells. In a flow cytometric study, IgM was expressed on the cell surface. In conclusion, an abnormality in a single gene may have decreased secretion of immunoglobulin from the B cells and the AM phagocytotic activity in the patient.

Does prolonged oral treatment with sustained-release morphine tablets influence immune function?

Opioids such as morphine are the mainstay of acute and chronic pain treatment. The purpose of this study was to investigate the immunosuppressive effects of morphine in patients with pain syndromes. We investigated 10 patients with chronic pain syndromes undergoing treatment with oral sustained-release morphine (30-240 mg/d) before and after 1,4, and 12 wk of treatment compared with healthy control subjects without morphine treatment. Immunological variables of the cellular and humoral immune axis showed that 1) total lymphocyte counts and the distribution of lymphocyte subpopulations, including helper T-cell/suppressor cytotoxic T-cell ratios (CD4/CD8 ratios), did not change compared with baseline or healthy control subjects; 2) proliferation of peripheral mononuclear cells (PMC) was not impaired by morphine treatment; 3) interleukin 2 production increased after 4 wk of treatment with morphine; and 4) immunoglobulin (Ig) production was reduced before initiation of therapy in pain patients and decreased further during morphine treatment, whereas Ig concentrations in the circulation remained at normal levels. These results indicate that treatment with oral, sustained-release morphine does not have a suppressive effect on overall PMC function. On the other hand, Ig production was impaired in patients with chronic pain and was further suppressed by morphine. Whether this suppression of humoral immune function has a clinical impact on the immune system as a whole remains to be determined. Treatment of patients with chronic pain with oral, sustained-release morphine does not influence cellular immune function, but it suppresses the already attenuated production of immunoglobulins.

Does Prolonged Oral Treatment with Sustained-Release Morphine Tablets Influence Immune Function?

Opioids such as morphine are the mainstay of acute and chronic pain treatment.The purpose of this study was to investigate the immunosuppressive effects of morphine in patients with pain syndromes. We investigated 10 patients with chronic pain syndromes undergoing treatment with oral sustained-release morphine (30-240 mg/d) before and after 1, 4, and 12 wk of treatment compared with healthy control subjects without morphine treatment. Immunological variables of the cellular and humoral immune axis showed that 1) total lymphocyte counts and the distribution of lymphocyte subpopulations, including helper T-cell/suppressor cytotoxic T-cell ratios (CD4/CD8 ratios), did not change compared with baseline or healthy control subjects; 2) proliferation of peripheral mononuclear cells (PMC) was not impaired by morphine treatment; 3) interleukin 2 production increased after 4 wk of treatment with morphine; and 4) immunoglobulin (Ig) production was reduced before initiation of therapy in pain patients and decreased further during morphine treatment, whereas Ig concentrations in the circulation remained at normal levels. These results indicate that treatment with oral, sustained-release morphine does not have a suppressive effect on overall PMC function. On the other hand, Ig production was impaired in patients with chronic pain and was further suppressed by morphine. Whether this suppression of humoral immune function has a clinical impact on the immune system as a whole remains to be determined. Implications: Treatment of patients with chronic pain with oral, sustained-release morphine does not influence cellular immune function, but it suppresses the already attenuated production of immunoglobulins.

Cellular and Humoral Immune Responses to Vascular Components in Thromboangiitis Obliterans

Cellular and humoral immune responses to vascular components were studied in 10 patients with thromboangiitis obliterans (TAO), including 3 in the mild stage of the disease and 7 in the active or severe stage. In this study the authors used the following vascular components: collagen Types I, III, IV, and V; elastin; and laminin. The cell-mediate reactivity (CMR) to these proteins was measured with an antigen-specific proliferation of peripheral mononuclear cells and evaluated by the stimulation index (SI), which is the ratio of thymidine incorporation in the presence and in the absence of antigen. The humoral immunologic response (HIR) to these vascular components was measured by an enzyme-linked immunosorbent assay (ELISA) and evaluated by the optical density (OD) index, which is the ratio of optical density (OD) in the patients' serum to that in the healthy male controls' serum. The stimulation index of collagen Types I and IV was significantly higher in patients with TAO than in healthy controls (p < 0.02). CMR to collagen Type V, elastin, and laminin was high in patients with active or severe TAO as well. However, similar statistical differences in mild TAO did not exist in the CMR. The OD index in collagen Types I, IV, and V was statistically higher in the patients than in the healthy controls (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous proliferation of peripheral mononuclear cells in natural measles virus infection: Identification of dividing cells and correlation with mitogen responsiveness

Spontaneous proliferation of peripheral mononuclear cells is pronounced following measles virus infection at a time when patients mount effective humoral and cell-mediated immune responses and manifest a range of poorly understood immunologic abnormalities. We found spontaneous activity (measles 8000 ± 1200 cpm vs control 1900 ± 350 cpm; P < 0.05) to wax and wane abruptly during the first week after the rash in parallel with expression of the lymphocyte activation marker OKT10. At peak activity, approximately 10% of circulating mononuclear cells were actively synthesizing DNA. Double labeling of individual mononuclear cells with autoradiography and immunoperoxidase demonstrated that B and T lymphocytes as well as monocytes participate in the spontaneous activity. Proliferative activity was increased 3- to 20-fold over control levels in all PBMC subsets such that close to one-third of circulating B cells and monocytes and 5–10% of CD4- and CD8-positive T cells were preparing to divide. Mitogen responsiveness was generally decreased in measles patients (58,800 ± 4600 cpm vs control 97,700 ± 15,500 cpm; P < 0.002). Neither spontaneous proliferation nor mitogen responsiveness was correlated with age, sex, or the presence of complications. Patients with the lowest mitogen responses, however, had the greatest increases in B cell ( P < 0.03) and CD8-positive T cell ( P < 0.05) proliferation. These data demonstrate that all major immunologic cell types proliferate in response to measles virus infection. Mechanisms by which spontaneous proliferative activity in individual mononuclear subsets could contribute to depressed mitogen responsiveness are discussed.

Theophylline and the immune response: In vitro and in vivo effects

We analyzed the in vitro and in vivo effects of theophylline on various immunological parameters including proliferation of peripheral mononuclear cells (PMNC) in response to phytohemagglutinin (PHA), anti-T3 and anti-T11 monoclonal antibodies (MAb), PHA-induced interleukin-2 (IL-2) and interferon-γ (IFN-γ) production by PMNC, interleukin-1 (IL-1) production by accessory cells, PHA-induced IL-2 production by T-cell clones, and PHA- and anti-T3 MAb-induced DNA synthesis by T cell clones. Results showed that theophylline inhibited PHA- and anti-T3-induced proliferation of both PMNC and T-cell clones, whereas the PMNC proliferation induced by MAb anti-T11 was not affected. The inhibition appeared to be dose-dependent and strictly related to the presence of the drug in the culture. Moreover, PHA-induced IL-2 production by both PMNC and T-cell clones also appeared to be reduced by theophylline. IL-1 production by accessory cells was not affected. These data suggest that the immunological inhibition exerted by theophylline is confined to the T-cell compartment, mainly by acting on structure(s) related to the T3 Ti complex, the primary site for T-cell activation. The alternative pathway of T-cell activation (i.e., via T11 site) seems unaffected. In addition, these results suggest possible clinical relations between the inhibition of the immune response and the plasma levels of the drug reached after a “once daily” or “twice daily” oral ingestion of slow-release theophylline products.

Fenoterol effects on the in vitro immune response

Beta-2-adrenergic agonists are often employed in the treatment of acute bronchostenosis. Following our recent investigations into the influence of some drugs (cromolyn, ketotifen, theophylline) on the immune response, in this study we analyzed the in vitro effects of fenoterol (β-2-adrenergic agonist) on the immune response. The mitogen-(PHA)-induced proliferation of peripheral mononuclear cells (PMNC), the PMNC proliferation induced by anti-T3 and anti-T11 monoclonal antibodies (MAbs), the PHA-induced lymphokine — interleukin 2 (IL-2) and interferon-gamma (IFN-γ) — production were studied in ten healthy volunteers. Since the plasmatic peak of fenoterol following a single inhalation of 200 μg is about 20 ng/ml, in the experiments herein reported the drug was tested in the cultures at concentrations lower, equal and higher than the plasmatic peak: respectively, 2, 20 and 200 ng/ml. Furthermore, for a more detailed study of T-lymphocyte activities, we also evaluated the effect of fenoterol on T-cell clone proliferation. Our results, which reveal no effects of fenoterol on the studied immunological parameters, acquire relevance when related to our previous reports showing a depression of the immunological response exerted by theophylline and ketotifen.

Immunoreconstitution of T-cell impairments in asymptomatic male homosexuals by Thymic Humoral Factor (THF)

The feasibility of using Thymic Humoral Factor (THF) for immunomodulation in asymptomatic male homosexuals was evaluated in a study on fifteen subjects with T-cell impairments, selected on the basis of a 2SD reduction in T helper/inducer (T4+) cells and one additional lymphocytic defect. Following two biweekly courses of treatment, mean relative increments of T4+ ( P <0.002), T3+ ( P <0.02) and total lymphocyte ( P <0.05) populations of the group receiving THF ( n = 7) were significantly increased when compared to the placebo group ( n = 8). In addition, a transient increase in T4+ lymphocytes was observed after the first course in the two individuals of the THF-treated group who were seropositive for HTLV-III/ LAV but not in those who were seronegative. No difference was found between the groups in fluctuations of serum interferon (IFN) or proliferation of peripheral mononuclear cells to mitogens. The results of this limited trial demonstrate that THF is capable of correcting T-cell impairments that may predispose asymptomatic homosexuals to infection by HTLV-III, without affecting IFN production. These findings suggest that future strategies for AIDS prevention in high-risk groups should include institution of large controlled trials in immunodeficient, asymptomatic, HTLV III/LAV-seronegative male homosexuals to study the potential of selective immunoreconstitution as a preventive measure against HTLV-III/LAV infection.