scholarly journals Recombinant interleukin-2 infusions and decreased IgG2 subclass concentrations [see comments]

Blood ◽  
1995 ◽  
Vol 85 (4) ◽  
pp. 925-928 ◽  
Author(s):  
RJ Soiffer ◽  
C Murray ◽  
J Ritz ◽  
N Phillips ◽  
D Jacobsohn ◽  
...  
Keyword(s):  
Human Serum ◽  
Nk Cells ◽  
Geometric Mean ◽  
Interleukin 2 ◽  
Malignant Neoplasms ◽  
Time Interval ◽  
Igg Subclass ◽  
Allogeneic Bone ◽  
Serum Igg ◽  
Recombinant Interleukin 2

The administration of low doses of recombinant interleukin-2 (rIL-2) in vivo to patients with malignant neoplasms has been demonstrated to selectively increase the number of circulating natural killer (NK) cells in these patients. Recent evidence from SCID mouse models suggests that IgG subclass levels can be influenced by the presence and activity of NK cells. Therefore, we sought to examine the effect of rIL- 2 infusions on human serum IgG subclass concentrations. We determined serum IgG subclass concentrations in 27 cancer patients receiving low- dose rIL-2 by daily continuous intravenous infusion. Eleven of these patients had active, metastatic, nonhematologic tumors; 16 patients had received IL-2 when they were in a minimal residual disease state after autologous or allogeneic bone marrow transplantation. Samples obtained before beginning IL-2 therapy and 8 to 10 weeks into therapy were tested. Treatment with IL-2 resulted in an increase in the percentage of CD56+ NK cells from 18% to 54% (P = .0001). A significant decrease in geometric mean IgG2 concentration from 2,017 micrograms/mL to 1,655 micrograms/mL was noted over this time interval (P = .03). Furthermore, the geometric mean IgG2 concentration after treatment was significantly lower than that of healthy controls (P = .026). In contrast, no significant changes in serum IgG1, IgG3, or IgG4 were noted during r- IL2 infusions. Our data suggest that rIL-2 treatment selectively decreases serum IgG2 concentrations. We speculate that increased NK cells mediate downregulation of human serum IgG2.

scholarly journals Recombinant interleukin-2 infusions and serum IgG subclass levels [letter; comment]

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 841-843 ◽  
Author(s):  
P Aucouturier ◽  
JL Preud'homme ◽  
WH Fridman ◽  
C Mathiot
Keyword(s):  
Interleukin 2 ◽  
Igg Subclass ◽  
Serum Igg ◽  
Letter Comment ◽  
Recombinant Interleukin 2

scholarly journals The effects of recombinant interleukin 2-activated natural killer cells on autologous peripheral blood hematopoietic progenitors.

1988 ◽  
Vol 168 (1) ◽  
pp. 47-54 ◽  
Author(s):  
A Nagler ◽  
P L Greenberg ◽  
L L Lanier ◽  
J H Phillips
Keyword(s):  
Nk Cells ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Residual Tumor ◽  
Myelogenous Leukemia ◽  
Hematopoietic Reconstitution ◽  
Recombinant Interleukin 2 ◽  
Acute Myelogenous

In the present study, we demonstrate that resting and rIL-2-activated NK cells had no inhibitory effects on peripheral blood-derived hematopoietic progenitor (HP) cells. Peripheral blood HP cells were similar to bone marrow progenitors in phenotype and clonogenic colony formation capabilities. Peripheral blood HP cells could be cocultured in vitro with rIL-2-activated autologous NK cells for 3 d without adverse effects on the HP cells. Acute myelogenous leukemia patients in stable remission were shown to have normal percentages of NK cells and elevated percentages of peripheral blood HP cells. NK cells from most of these patients could be activated with rIL-2 to lyse fresh uncultured tumor cells as well as autologous leukemia cells without effecting the peripheral blood HP cells. These results suggest that rIL-2-activated NK cells may be used to purge peripheral blood HP cell preparations of residual tumor cells before hematopoietic reconstitution.

Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

1991 ◽  
Vol 9 (12) ◽  
pp. 2110-2119 ◽  
Author(s):  
M A Caligiuri ◽  
C Murray ◽  
R J Soiffer ◽  
T R Klumpp ◽  
M Seiden ◽  
...  
Keyword(s):  
Nk Cells ◽  
Advanced Cancer ◽  
Low Dose ◽  
Interleukin 2 ◽  
Outpatient Setting ◽  
Lak Cells ◽  
Phase Ii Studies ◽  
Recombinant Interleukin 2

In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.

scholarly journals Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1092-1097 ◽  
Author(s):  
D Blaise ◽  
D Olive ◽  
AM Stoppa ◽  
P Viens ◽  
C Pourreau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Autologous Bone Marrow ◽  
Hematologic Toxicity ◽  
Allogeneic Bone ◽  
Recombinant Interleukin 2 ◽  
Autologous Bone

T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL- 2 after autologous BMT leading to a major immune activation 2.5 months after BMT.

scholarly journals Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 907-914
Author(s):  
S Skettino ◽  
J Phillips ◽  
L Lanier ◽  
A Nagler ◽  
P Greenberg
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
T Cell ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Inhibitory Activity ◽  
Interleukin 2 ◽  
Gm Csf ◽  
Recombinant Interleukin 2

Because T lymphocytes and natural killer (NK) cells produce a variety of growth factors and interleukin 2 (IL2) modulates the activity of both, we assessed the ability of IL2 to stimulate human T cells and NK cells to produce hematopoietic growth factors detectable in clonogenic marrow culture. Human recombinant interleukin 2 (rIL2) added directly to cultures of human bone marrow that had been depleted of monocytes or depleted of both monocytes and T cells caused no significant alteration of myeloid (CFU-GM) or erythroid colony formation. Conditioned media harvested from rIL2-stimulated (greater than 100 U/mL) peripheral blood mononuclear cells, T cells, Leu-2 cells, and Leu-3 cells all had erythroid burst-promoting activity (BPA) but lacked myeloid colony- stimulating factor (GM-CSF) or CFU-GM-inhibitory activity. These T cells were IL2 receptor-negative, and the addition of anti-IL2 receptor monoclonal antibody (anti-Tac) to T cell cultures did not abrogate this IL2-stimulated BPA production. In addition, Percoll gradient-enriched, large granular lymphocytes (LGL) were separated by fluorescence- activated cell sorting into Leu-11+ (NK) cells and Leu-11- (low-density Leu-4+ T) cell fractions. rIL2 stimulated LGL, Leu-11+ and Leu-11- cells to produce BPA but not detectable GM-CSF or CFU-GM-inhibitory activity. Leu-11+ (NK) cells were Tac-negative from days 0 through 14 of culture. We conclude that rIL2 at high concentrations stimulated T cells, Leu-2 and Leu-3 cell subsets, LGL, and NK cells to produce BPA but not GM-CSF and that this stimulation may be mediated by an IL2 receptor distinct from Tac or by an epitope of the IL2 receptor not recognized by the anti-Tac antibody.

scholarly journals Generation of natural killer cells from both Fc gamma RII/III+ and Fc gamma RII/III- murine fetal liver progenitors

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1453-1462 ◽  
Author(s):  
P Moingeon ◽  
HR Rodewald ◽  
D McConkey ◽  
A Mildonian ◽  
K Awad ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Fetal Liver ◽  
Gradient Centrifugation ◽  
Interleukin 2 ◽  
Surface Expression ◽  
In Vitro Expansion ◽  
Recombinant Interleukin 2 ◽  
Intrathymic Injection

In vitro culture of day-15.5 murine fetal liver (FL) cells in the presence of recombinant interleukin-2 (IL-2) results in the expansion of Fc gamma RII/III+ CD3-Ti-NK1.1+ cells displaying both natural killer (NK) and antibody-dependent cell cytotoxicity (ADCC) cytolytic activities. These FL-derived NK cells express Fc gamma RIII (CD16) in association with an Fc epsilon RI gamma homodimer on their surface. In contrast, in vitro expansion of FL cells in the absence of IL-2 generates noncytotoxic cells belonging to the myelomonocytic lineage (Mac1+Gr1+NK1.1-). Hence, IL-2 appears to be critical for the proliferation and differentiation of NK cells from FL progenitors. Experiments in which FL cells were fractionated by density gradient centrifugation before in vitro expansion showed that NK progenitors are contained within a cell population with a density of 1.04 < d < 1.08 g/mL. Cells with d > 1.08 g/mL (representing > or = 40% of FL cells) have no such NK progenitor activity. In addition, after intrathymic injection into Ly5 congenic host animals, day-15.5 CD4-CD8- FL cells mature into CD4+CD8+ thymocytes within 12 days. Interestingly, this T- cell progenitor activity is restricted to subpopulations of FL cells that also contain NK progenitors, but is absent in high-density (d > 1.08 g/mL) FL cells. Finally, fractionation of FL cells according to surface expression of Fc gamma RII/III complexes shows that NK (and T- lymphocyte) progenitors are found in both Fc gamma RII/III+ and Fc gamma RII/III-FL subpopulations.

scholarly journals Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 907-914 ◽  
Author(s):  
S Skettino ◽  
J Phillips ◽  
L Lanier ◽  
A Nagler ◽  
P Greenberg
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
T Cell ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Inhibitory Activity ◽  
Interleukin 2 ◽  
Gm Csf ◽  
Recombinant Interleukin 2

Abstract Because T lymphocytes and natural killer (NK) cells produce a variety of growth factors and interleukin 2 (IL2) modulates the activity of both, we assessed the ability of IL2 to stimulate human T cells and NK cells to produce hematopoietic growth factors detectable in clonogenic marrow culture. Human recombinant interleukin 2 (rIL2) added directly to cultures of human bone marrow that had been depleted of monocytes or depleted of both monocytes and T cells caused no significant alteration of myeloid (CFU-GM) or erythroid colony formation. Conditioned media harvested from rIL2-stimulated (greater than 100 U/mL) peripheral blood mononuclear cells, T cells, Leu-2 cells, and Leu-3 cells all had erythroid burst-promoting activity (BPA) but lacked myeloid colony- stimulating factor (GM-CSF) or CFU-GM-inhibitory activity. These T cells were IL2 receptor-negative, and the addition of anti-IL2 receptor monoclonal antibody (anti-Tac) to T cell cultures did not abrogate this IL2-stimulated BPA production. In addition, Percoll gradient-enriched, large granular lymphocytes (LGL) were separated by fluorescence- activated cell sorting into Leu-11+ (NK) cells and Leu-11- (low-density Leu-4+ T) cell fractions. rIL2 stimulated LGL, Leu-11+ and Leu-11- cells to produce BPA but not detectable GM-CSF or CFU-GM-inhibitory activity. Leu-11+ (NK) cells were Tac-negative from days 0 through 14 of culture. We conclude that rIL2 at high concentrations stimulated T cells, Leu-2 and Leu-3 cell subsets, LGL, and NK cells to produce BPA but not GM-CSF and that this stimulation may be mediated by an IL2 receptor distinct from Tac or by an epitope of the IL2 receptor not recognized by the anti-Tac antibody.

Lymphopenia as an indication for the use of recombinant interleukin-2

2020 ◽  
pp. 32-54
Author(s):  
V. N. Egorova ◽  
I. V. Babachenko ◽  
O. A. Gisinger ◽  
K. S. Titov
Keyword(s):  
Opportunistic Infections ◽  
Adverse Outcome ◽  
Interleukin 2 ◽  
Malignant Neoplasms ◽  
Statistical Assessment ◽  
Pathological Conditions ◽  
Autoimmune Pathology ◽  
The World ◽  
Recombinant Interleukin 2 ◽  
Regulatory Effects

Pathogenetic aspects of lymphopenia in various pathological conditions are studied. A statistical assessment of the incidence of lymphopenia in the world is given. It is shown that prolonged lymphopenia increases the risk of developing diseases of infectious genesis and an adverse outcome. A long-existing decrease in lymphocytes leads to the activation of opportunistic infections and becomes the basis for the development of malignant neoplasms and autoimmune pathology. Recombinant interleukin 2 (Roncoleukin®), filling the deficiency of endogenous interleukin 2, is a means of not only substitution, but also of inductive therapy. Restoring the regulatory effects of interleukin 2, Roncoleukin® levels the manifestations of lymphopenia and positively affects the dynamics and outcome of the disease.

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