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Cancer Biotherapy & Radiopharmaceuticals Dec 2000The ideal treatment for HIV infections would supplement highly active antiretroviral therapy (HAART) started at the time of initial diagnosis with an agent that can... (Review)
Review
The ideal treatment for HIV infections would supplement highly active antiretroviral therapy (HAART) started at the time of initial diagnosis with an agent that can facilitate cure in the briefest time possible to avoid adverse effects of extended HAART such as drug toxicity, noncompliance, and shortened telomere-induced replicative senescence of CD8 cells. As a crucial part of the regimen, the agent must be able to initiate killer reactions against the HIV, replenish CD4 cells, rejuvenate CD8 cells, block HIV invasion of CD4 cells, activate latent HIV-sequestering host cells, stimulate effective immune reactions against malignancies, generate effective immune responses against conventional and opportunistic infections, circumvent the treatment- and immune response-evading capacities of HIV mutations, and reconstitute immune and hematopoietic competences. Over the past decade, the L4 isolectin of PHA has been presented as a mitogen capable of meeting these goals as they have become defined, but its potential has not been recognized sufficiently to expedite its evaluation. Pokeweed mitogen (PWM) offers the major advantage of being up to 500 times more potent than PHA and has much smaller molecular weight (22,500 to 38,000 daltons versus approximately 125,000 daltons). Given by injection, it has demonstrated curative effects for metastatic malignancies in dogs and cats unassisted by ancillary therapy. Unlike PHA, PWM does not block the attachment of HIV gp 120 to CD4 membrane receptors, but it can obstruct CD4 cell invasion by binding with the CD4 receptors themselves. An expeditious manner of applying PWM would be to give minute doses of an ultra potent root extract capable of inducing a benign plasmacytoid lymphoblastic leukemoid reaction that reverses spontaneously after about 10 weeks. This might prove curative given in conjunction with HAART or possibly even without it. The preferred route of administration for the mitogens in humans would be intravenous although oral administration might prove more advantageous, particularly with PWM. These mitogens might be used singly or, if necessary, in combination after the toxicities have been carefully delineated in humans. Economic forces might restrict treatment availability solely to orally administered PWM therapy in poverty-stricken undeveloped countries if this were shown to be curative. These proposals originating from the authors long concerned with mitogen management of various disorders including HIV infections but only peripherally involved with their clinical applications, are offered for consideration by investigators perceptive enough to see the wisdom of exploring the curative possibilities.
Topics: Adjuvants, Immunologic; Animals; HIV Infections; Humans; Immunotherapy; Phytohemagglutinins; Pokeweed Mitogens
PubMed: 11190495
DOI: 10.1089/cbr.2000.15.629 -
Cancer Biotherapy & Radiopharmaceuticals Oct 2002
Review
Topics: Concanavalin A; HIV Infections; Humans; Immunization; Mitogens; Neoplasms; Phytohemagglutinins; Pokeweed Mitogens; Skin Tests
PubMed: 12470427
DOI: 10.1089/108497802760804808 -
Immunology Jun 1980Human peripheral blood mononuclear cells were stimulated with pokeweed mitogen (PWM) to study the role of mononuclear phagocytic cells (MNP) in lymphocyte proliferation....
Human peripheral blood mononuclear cells were stimulated with pokeweed mitogen (PWM) to study the role of mononuclear phagocytic cells (MNP) in lymphocyte proliferation. MNP were identified by cytoplasmic alpha-naphthyl acetate esterase, by the capacity of phagocytosis and by lysozyme synthesis. It appeared that after 3 days of stimulation with PWM all MNP disappeared from the cultures and remained absent during prolonged culture in mitogen-free medium. In non-stimulated cultures MNP remained. The disappearance of MNP from cell cultures was caused by a lymphocyte-derived factor, which was transferable by cell-free supernatants of stimulated mononuclear cells. From experiments in which cultures were treated with different concentations of PWM and from pre-culture experiments, it could be shown that in vitro lymphocyte proliferation required both non-stimulated lymphocytes and freshly prepared MNP. In addition, the decreasing concentration of PWM as stimulating agent, resulted in a decreasing proliferation of lymphocytes, which was inversely proportional to the presence of MNP.
Topics: Cell Division; Cells, Cultured; Humans; Lymphocyte Activation; Muramidase; Naphthol AS D Esterase; Phagocytes; Phagocytosis; Pokeweed Mitogens; Time Factors
PubMed: 7409856
DOI: No ID Found -
The American Review of Respiratory... Aug 1982The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay....
The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay. Unfractionated peripheral blood mononuclear cells from 7 nonsmoking normal subjects responded to pokeweed mitogen with a geometric mean of 6,550 Ig-secreting cells per million cultured mononuclear cells, whereas monocyte-depleted mononuclear cells responded with only 148 (p = 0.015, paired 2-tailed t test). The addition of 1 to 20% autologous bronchoalveolar cells to unfractionated mononuclear cells progressively suppressed the Ig-secretory response (p less than 0.01, paired t test comparing 0 to greater than or equal to 10% added bronchoalveolar cells). However, the addition of low concentrations of bronchoalveolar cells to monocyte-depleted mononuclear cells partially reconstituted the response to pokeweed mitogen, whereas the response with higher concentrations of bronchoalveolar cells was similar to background responses. Thus bronchoalveolar cells could modulate pokeweed-nitrogen-induced Ig secretion in different ways, depending on the pressure or absence of monocytes in the mononuclear cell population. The suppressor activities of bronchoalveolar cells were not abrogated by prior irradiation and were only partially reversed by the addition of indomethacin to the cultures. However, prior disruption of bronchoalveolar cells completely abolished their suppressive functions. Suppression of pokeweed-mitogen-induced Ig secretion is probably mediated by intact, radioresistant pulmonary alveolar macrophages.
Topics: Adult; Bronchi; Female; Humans; Immunoglobulins; In Vitro Techniques; Leukocytes; Macrophages; Male; Pokeweed Mitogens; Pulmonary Alveoli; T-Lymphocytes, Regulatory
PubMed: 6213186
DOI: 10.1164/arrd.1982.126.2.248 -
Journal of Applied Physiology... Dec 2019Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is...
Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [, , , and after intensive care unit (ICU) admission] determined in patients with sepsis ( = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, = 10). In a second cohort, expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV ( = 0.01), OKT3 ( = 0.02), and PWM ( = 0.02 on ), whereas unstimulated IFNγ secretion did not differ. expression was also significantly decreased in patients with sepsis at all time points ( = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis. We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.
Topics: Adult; Aged; Cytomegalovirus; Female; Humans; Interferon-gamma; Leukocytes, Mononuclear; Male; Middle Aged; Muromonab-CD3; Pokeweed Mitogens; Sepsis
PubMed: 31545153
DOI: 10.1152/japplphysiol.00438.2019 -
Clinical and Experimental Immunology Apr 1980The generation of immunoglobulin-producing cells from human peripheral blood lymphocytes in pokeweed mitogen-simulated cultures was significantly suppressed by...
The generation of immunoglobulin-producing cells from human peripheral blood lymphocytes in pokeweed mitogen-simulated cultures was significantly suppressed by levamisole. Greatest suppression was observed when cells were incubated with levamisole at a concentration of 10(-6) M for 20 min or more prior to culture. Such suppression occurred when untreated as well as levamisole-treated B cells were co-cultured only with levamisole-treated T cells. Adding of levamisole-treated T cells to a combination of untreated autologous B and T cells resulted in the suppression of B cell differentiation. The results suggest that levamisole treatment of lymphocytes exerts suppression on pokeweed mitogen-induced B cell differentiation through its effect on T cell regulatory properties.
Topics: Adult; B-Lymphocytes; Cell Differentiation; Cells, Cultured; Humans; Levamisole; Mitosis; Pokeweed Mitogens; T-Lymphocytes, Regulatory
PubMed: 6446431
DOI: No ID Found -
Current Pharmaceutical Biotechnology 2019Interferon-gamma release assays (IGRAs) are blood tests used to measure the amount of interferon-γ (IFN-γ) released by T lymphocytes after stimulation by antigens...
BACKGROUND
Interferon-gamma release assays (IGRAs) are blood tests used to measure the amount of interferon-γ (IFN-γ) released by T lymphocytes after stimulation by antigens specific for the diagnosis of latent tuberculosis infection. A mitogen serves as a positive control to assess the immune function in IGRAs.
METHODS
This in vitro study was conducted to evaluate IFN-γ production by human whole blood stimulated with heat-treated and/or cation-supplemented phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), using QuantiFERON-TB Gold Kit ELISA tests.
RESULTS
The optimal concentrations of PWM, Con A and PHA for IGRAs were 2 µg/mL, 5 µg/mL and 10 µg/mL, respectively. The results showed that IFN-γ production in response to PWM was the highest and PHA was the lowest amount. The median values of three mitogens were in the following order: PWM≥Con A≥ positive control>>PHA-P>>negative control. PWM and PHA were heat stable, while Con A was heat sensitive. The mitogen response of lymphocytes to untreated or heat-treated PWM and heat-treated Con A was increased in 1 mM Ca2+-supplemented groups, whereas the response to heat-treated PHA was decreased. Exposure to 1 mM Mg2+ had no effect on untreated or heat-treated PWM, and a concentration of 1 mM Zn2+ inhibited the stimulation of un-treated PWM. We found that calcium supplementation improved the PWM-induced production of IFN-γ.
CONCLUSION
Therefore, PWM is an appropriate mitogen for use as a positive control in IGRAs. It is a potential indicator of cytokine production in the diagnostic as well as research settings, and calcium supplementation improved stimulation.
Topics: Adult; Aged; Cations; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Hot Temperature; Humans; Interferon-gamma; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; Tuberculosis, Pulmonary; Young Adult
PubMed: 31132974
DOI: 10.2174/1389201020666190528093432 -
Bioscience, Biotechnology, and... Jul 2004We investigated native structures and mitogenic properties of pokeweed lectin-D isoforms (PL-D1 and -D2) on human peripheral blood lymphocytes along with other...
We investigated native structures and mitogenic properties of pokeweed lectin-D isoforms (PL-D1 and -D2) on human peripheral blood lymphocytes along with other isolectins (PL-A to -C). Both native PL-D isoforms appeared to behave as monomers. PL-D2 proliferated the lymphocytes like PL-C, whereas PL-D1 had no mitogenicity. PL-D1 acquired mitogenic activity after trimming of the C-terminal dipeptide.
Topics: Cell Proliferation; Dose-Response Relationship, Drug; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Mitosis; Pokeweed Mitogens; Protein Isoforms; Ribosome Inactivating Proteins; Tetrazolium Salts
PubMed: 15277769
DOI: 10.1271/bbb.68.1591 -
Agents and Actions Aug 1988The interaction between pokeweed mitogen (PWM) and peripheral blood mononuclear cells (PBMC) was investigated using rabbit anti-PWM antiserum (anti-PWM) and 125I-PWM....
The interaction between pokeweed mitogen (PWM) and peripheral blood mononuclear cells (PBMC) was investigated using rabbit anti-PWM antiserum (anti-PWM) and 125I-PWM. Incubation of PBMC with PWM in the presence of anti-PWM resulted in an inhibition of the mitogenic effect of PWM. Anti-PWM predominantly blocked the interaction of PWM with monocytes, which is essential for optimal stimulation of lymphoid cells with PWM. Addition of anti-PWM to PBMC at several time-points after incubation with PWM showed inhibition of mitogenic activity when anti-PWM was added within 8 hours. However, enhancement of PWM-induced blast cell formation was found when anti-PWM was added after 48 hours. Further analysis revealed that the inhibition of PWM stimulation was mediated by the F(ab')2 part of anti-PWM IgG. On the other hand F(ab')2-anti-PWM was not able to enhance the effect of PWM. Incubation of PBMC with 125I-PWM and anti-PWM simultaneously, decreased the binding of PWM to both lymphocytes and monocytes. In contrast, addition of anti-PWM 48 hours after the incubation of PBMC with PWM resulted in an increased binding of PWM to monocytes. These results show that anti-PWM can modulate the lymphocyte reaction to PWM and suggest two possible mechanisms by which PWM can stimulate PBMC, both of which are dependent on the interaction of PWM with monocytes.
Topics: Antibodies; Humans; Immunoglobulin Fab Fragments; In Vitro Techniques; Leukocytes, Mononuclear; Lymphocyte Activation; Monocytes; Pokeweed Mitogens
PubMed: 3189039
DOI: 10.1007/BF01969101 -
Clinical Immunology and Immunopathology Nov 1990The thymus, with its striking B cell infiltrates, is widely regarded as an important element in the pathogenesis of myasthenia gravis (MG) but its role remains to be... (Comparative Study)
Comparative Study
Pokeweed mitogen-induced immunoglobulin secretory responses of thymic B cells in myasthenia gravis: selective secretion of IgG versus IgM cannot be explained by helper functions of thymic T cells.
The thymus, with its striking B cell infiltrates, is widely regarded as an important element in the pathogenesis of myasthenia gravis (MG) but its role remains to be elucidated. To gain further insight into the functional properties of MG thymic B cells, we studied the heavy chain isotype of immunoglobulin they produced in vitro in response to the T cell-dependent polyclonal activator pokeweed mitogen (PWM). MG thymic cells secreted prominent amounts of IgG but little IgM. In contrast, peripheral blood mononuclear cells (PBM) of the same subjects secreted similar amounts of IgG and IgM as did PBM of control subjects. In cell admixture experiments, MG thymic T cells, like PBM T cells, helped autologous PBM B cells produce IgM as well as IgG, although the overall magnitude of help for both isotypes appeared less than that of PBM T cells. Thus, in response to PWM, MG thymic B cells are largely committed to an IgG response and this likely reflects the intrinsic properties of these cells rather than the immunoregulatory properties of thymic T cells. This IgG isotype switch likely reflects in vivo activation events.
Topics: Adult; Antibody-Producing Cells; B-Lymphocytes; Humans; Immunoglobulin Isotypes; Myasthenia Gravis; Pokeweed Mitogens; T-Lymphocytes, Helper-Inducer; Thymus Gland
PubMed: 2145106
DOI: 10.1016/0090-1229(90)90035-o