Dietary Nucleotide Effects upon Immune Function in Infants

PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 359-363
Author(s):  
Jane D. Carver ◽  
Bernardo Pimentel ◽  
William I. Cox ◽  
Lewis A. Barness
Keyword(s):  
Human Milk ◽  
Immune Function ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Nonprotein Nitrogen ◽  
Term Infants ◽  
Group Rate ◽  
Breast Fed ◽  
Normal Immune Function

Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast-fed and NT+ groups compared with the NT- group (41.7 ± 4.7, 32.2 ± 3.4, 21.7 ± 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 ± 0.28 U/mL, 0.27 ± 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant.

Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity.

1990 ◽  
Vol 8 (10) ◽  
pp. 1618-1629 ◽  
Author(s):  
R G Steis ◽  
W J Urba ◽  
L A VanderMolen ◽  
M A Bookman ◽  
J W Smith ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ovarian Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Patients ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Small Bowel Adenocarcinoma ◽  
Colorectal Cancer Patients

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.

scholarly journals Regulation of cytokine release from mononuclear cells by the iron- binding protein lactoferrin

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 235-240 ◽  
Author(s):  
SP Crouch ◽  
KJ Slater ◽  
J Fletcher
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Binding Protein ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Specific Antiserum ◽  
Iron Binding ◽  
Iron Binding Protein

Abstract The iron-binding protein lactoferrin (Lf) is a constituent of neutrophil secondary granules and is discharged into the surrounding medium when neutrophils are activated. Lf released from neutrophils phagocytosing opsonized particles inhibits proliferation of mixed lymphocyte cultures (MLC) and has also been shown to inhibit granulopoiesis, suppress antibody production, and regulate natural killer cell activity. All of these processes are controlled by cytokines, suggesting that Lf may modulate immune responses by inhibiting cytokine activity. When MLC were cultured in round-bottomed wells to crowd the cells together, Lf, 50% saturated with iron, inhibited both proliferation and interleukin-2 (IL-2) release into the supernatants. Inhibition was concentration-dependent and lost at concentrations of Lf greater than 10(-12) mol/L. Lf at 10(-10) mol/L inhibited release of tumor necrosis factor-alpha (TNF) and interleukin- 1 beta (IL-1) into MLC supernatants, as well as inhibiting IL-2 release. TNF in the supernatant was significantly reduced at 5 and 24 hours, becoming less and losing significance by 72 hours. IL-1 in the supernatant was not significantly reduced at 5 and 24 hours, becoming significant at 48 and 72 hours. IL-2 was significantly reduced at 48 and 72 hours and followed the same time course as proliferation. Inhibition was blocked by specific antiserum to Lf, but not by a preimmune serum. Lf, 10(-10) mol/L, also inhibited the production of TNF (49.15% +/- 7.98%; n = 10, P = .032) and IL-1 (42.67% +/- 6.72%; n = 6, P = .032) from endotoxin-stimulated mononuclear cells. As with MLC, inhibition was dose-dependent and abrogated by specific antiserum. Lf did not block the biological action of TNF, IL-1, or IL-2 in specific assays using cytokine-sensitive cell lines. These data suggest that Lf, released from activated neutrophils, acts as a negative feedback mechanism to prevent recruitment and activation of leukocytes in sites of inflammation.

Letter to the Editor

PEDIATRICS ◽  
1982 ◽  
Vol 70 (3) ◽  
pp. 499-500
Author(s):  
Frank R. Greer ◽  
Lorraine E. Reeve ◽  
Russell W. Chesney ◽  
Hector F. DeLuca
Keyword(s):  
Vitamin D ◽  
Human Milk ◽  
Vitamin D Supplementation ◽  
Full Term ◽  
Recommended Dietary Allowance ◽  
Term Infants ◽  
Letter To The Editor ◽  
Dietary Allowance ◽  
Breast Fed

We would like to thank Little and Chadwick for their comments. It is true that the vitamin D content of human milk is very low, supplying less than the daily recommended dietary allowance. As observed by Chadwick, the vast majority of full-term breast-fed infants at present do not develop rickets despite the lack of vitamin D supplementation. While we would agree with Little that rickets does occur in breast-fed infants, we cannot confirm or deny his observation that the majority of full-term infants who develop rickets at the present time are breast-fed.

Defective expression of the interleukin-2/interleukin-15 receptor β subunit leads to a natural killer cell–deficient form of severe combined immunodeficiency

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 877-879 ◽  
Author(s):  
Kimberly C. Gilmour ◽  
Hodaka Fujii ◽  
Treena Cranston ◽  
E. Graham Davies ◽  
Christine Kinnon ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Severe Combined Immunodeficiency ◽  
Interleukin 2 ◽  
Cytokine Signaling ◽  
Receptor Complex ◽  
Combined Immunodeficiency ◽  
Interleukin 15

Abstract Development of T and natural killer (NK) cells is critically dependent on cytokine signaling, and defects in cytokine receptor complex subunits have been shown to result in severe combined immunodeficiency (SCID) syndromes in humans and in murine models. An infant boy had typical clinical features of SCID and was found to lack NK cells in his peripheral circulation. Molecular analysis did not reveal abnormalities in his γc or JAK-3 genes, and he was investigated for defects in the interleukin-15 (IL-15) receptor complex because functional IL-15 signaling is essential for NK cell development. Expression of the IL-2R/IL-15Rβ chain was significantly reduced in the patient's peripheral blood mononuclear cells (PBMCs) by immunoblot, flow cytometry, and Northern blot analysis. Furthermore, IL-2 stimulation of PBMCs showed only minimal tyrosine phosphorylation of JAK-3. These data demonstrate that defects in IL-2R/1L-15Rβ expression can lead to a unique NK-deficient SCID immunophenotype.

scholarly journals Regulation of cytokine release from mononuclear cells by the iron- binding protein lactoferrin

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 235-240 ◽  
Author(s):  
SP Crouch ◽  
KJ Slater ◽  
J Fletcher
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Binding Protein ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Specific Antiserum ◽  
Iron Binding ◽  
Iron Binding Protein

The iron-binding protein lactoferrin (Lf) is a constituent of neutrophil secondary granules and is discharged into the surrounding medium when neutrophils are activated. Lf released from neutrophils phagocytosing opsonized particles inhibits proliferation of mixed lymphocyte cultures (MLC) and has also been shown to inhibit granulopoiesis, suppress antibody production, and regulate natural killer cell activity. All of these processes are controlled by cytokines, suggesting that Lf may modulate immune responses by inhibiting cytokine activity. When MLC were cultured in round-bottomed wells to crowd the cells together, Lf, 50% saturated with iron, inhibited both proliferation and interleukin-2 (IL-2) release into the supernatants. Inhibition was concentration-dependent and lost at concentrations of Lf greater than 10(-12) mol/L. Lf at 10(-10) mol/L inhibited release of tumor necrosis factor-alpha (TNF) and interleukin- 1 beta (IL-1) into MLC supernatants, as well as inhibiting IL-2 release. TNF in the supernatant was significantly reduced at 5 and 24 hours, becoming less and losing significance by 72 hours. IL-1 in the supernatant was not significantly reduced at 5 and 24 hours, becoming significant at 48 and 72 hours. IL-2 was significantly reduced at 48 and 72 hours and followed the same time course as proliferation. Inhibition was blocked by specific antiserum to Lf, but not by a preimmune serum. Lf, 10(-10) mol/L, also inhibited the production of TNF (49.15% +/- 7.98%; n = 10, P = .032) and IL-1 (42.67% +/- 6.72%; n = 6, P = .032) from endotoxin-stimulated mononuclear cells. As with MLC, inhibition was dose-dependent and abrogated by specific antiserum. Lf did not block the biological action of TNF, IL-1, or IL-2 in specific assays using cytokine-sensitive cell lines. These data suggest that Lf, released from activated neutrophils, acts as a negative feedback mechanism to prevent recruitment and activation of leukocytes in sites of inflammation.

scholarly journals Analysis of natural killer cells in patients with aplastic anemia

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1349-1355 ◽  
Author(s):  
P Gascon ◽  
N Zoumbos ◽  
N Young
Keyword(s):  
Aplastic Anemia ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Normal Range ◽  
Granular Lymphocytes

Abstract We have analyzed natural killer (NK) cells in 43 patients with severe aplastic anemia, using cytotoxicity assays and microfluorometry with monoclonal antibodies, prior to and after treatment with antithymocyte globulin (ATG). Before treatment, natural killer cell activity (NKa) in both peripheral blood and bone marrow was markedly decreased in 76% of patients as compared with normal controls. Although we have measured low NKa in patients receiving large numbers of blood transfusions (means = 150 U of RBCs), six aplastic patients had low NKa in the absence of transfusions, and the average number of transfusions in the total population was low (means = 24). Purification of larger granular lymphocytes (LGLs) from peripheral blood of aplastic anemia patients failed to recover significant NKa. Most of these large granular lymphocytes showed few azurophilic granules. NKa was appropriately enhanced in these patients samples by exposure of mononuclear cells to either interleukin 2 (IL-2) or interferon (IFN). Analysis of peripheral blood phenotypic markers showed that cells bearing Leu 7 antigen were in the normal range in aplastic anemia (means = 12% +/- 2%; normal = 16% +/- 2%), but there was a deficiency of Leu 11+ cells (means = 8% +/- 2%; normal = 15% +/- 2%). The number of Leu 11+ cells was well correlated with NKa. In 13 of 22 patients treated with ATG, NKa returned to the normal range, and recovery of NKa was correlated to hematopoietic recovery. Our results suggest that deficient NKa is an intrinsic feature of aplastic anemia, and that the circulating cells in this disease are of the pre-NK cell stage.

scholarly journals Microbiota–Muscle/–Immune Interactions in Rhesus Macaque under Simulated Weightlessness Revealed by Integrated Multi-Omics Analysis

2021 ◽  
Author(s):  
Peng Zhang ◽  
Libin Shao ◽  
Jie Zhang ◽  
Lu Wang ◽  
Huimei Yuan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gut Microbiota ◽  
Immune Function ◽  
Muscle Atrophy ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Health And Safety ◽  
Peripheral Blood Mononuclear ◽  
Omics Analysis ◽  
Wide Range

Abstract BackgroundLong-term exposure to microgravity during spaceflight has adverse effects on human health including muscle atrophy, impaired immune function, and alterations in gut microbiome profile. Gut microorganisms influence a wide range of host biological processes, but their interactions with skeletal muscle and the immune system under microgravity are not known. MethodsRhesus macaques (Macaca mulatta) were subjected to -6° head-down tilted bed rest (HDBR) for 6 weeks. Fecal samples, skeletal muscle tissue, and peripheral blood mononuclear cells (PBMCs) were collected for metagenomic, metabolomic, and transcriptomic analyses respectively and further integrated for a multi-omics analysis.ResultsHDBR resulted in significantly altered taxon abundance in 1 class, 5 orders, 11 families, 55 genera, and 122 species of microbes. We also identified the significantly changed metabolites in atrophied muscles, including some crucial metabolites (such as L-alanine and L-carnitine) and hub metabolites (such as pyridoxamine and epinephrine) involved in energy metabolism. Transcriptomic analysis of PBMCs revealed genes related to leukocyte activation, differentiation, and interleukin-2 production that were differentially expressed as a result of HDBR exposure. By integrating multi-omics analysis, we identified 3 bacterial genera (Klebsiella, Kluyvera, and Bifidobacterium) that were closely associated with immune dysfunction and 5 (including Oligella, Sporosarcina, Citrobacter, Weissella, and Myroide) that were associated with abnormal metabolism of amino acids in atrophied muscles induced by HDBR. Of note, the reduced abundance of butyrate-producing colon bacteria Eubacterium, Roseburia and their cross-feeding bacteria Bifidobacteria may contribute to both the impaired immune function and muscle atrophy caused by HDBR.ConclusionsWe first reported the HDBR-associated changes in gut microbiota composition, metabolomics of skeletal muscle and transcripts of PBMCs in non-human primate. Particularly, we revealed the underlying microbiota-muscle and microbiota-immune interactions during simulated microgravity, implicating that modulation of gut microbiota may represent a new strategy in enhancing crewmembers’ health and safety during long-term space expeditions.

The efficacy of CD3 x CD19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3208-3212 ◽  
Author(s):  
IA Haagen ◽  
AJ Geerars ◽  
WB de Lau ◽  
BJ Bast ◽  
BC de Gast
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Clonogenic Assay ◽  
Lymphoblastic Leukemia ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Antigen

To evaluate the potency by which human T cells are targeted and activated by bispecific monoclonal antibodies (BsAbs) to lyse tumor cells, a clonogenic assay was developed. The efficacy of a CD3 x CD19 BsAb binding to both the CD3 T-cell antigen and the CD19 B-cell antigen was already proven in 51Cr-release assays and in 3-day activation cultures. To achieve more quantitative results, a 14-day clonogenic assay, based on limiting-dilution, was performed for the determination of the initial and residual number of clonogenic units obtained with a CD19+ pre-pre-B acute lymphoblastic leukemia (ALL-B) cell line. Elimination of up to 5 logs of ALL-B cells by freshly isolated peripheral blood mononuclear cells (PBMCs) cultured with BsAb plus interleukin-2 (IL-2) could be detected. The presence of human IgG did not abolish the effect. Repeated addition of each of the two agents was necessary, because a single treatment produced only a 1- to 2-log kill. CD3 monoclonal antibody and IL-2 stimulation (“lymphokine-activated killer cell” conditions) resulted in only a 2-log kill. The number of T cells proved critical in lysis of ALL-B cells, with a 5-log kill using a T-cell:B-cell ratio of 3:1 but with only a 1-log kill using a ratio of 1:1. PBMCs isolated from patients with non-Hodgkin's lymphoma, both in relapse or remission, proved to be as competent as those from healthy donors in removing ALL-B cells. This clonogenic assay shows the importance of repeated administration of CD3 x CD19 BsAb and IL-2 and offers the possibility to compare it with other therapies in B-cell malignancy.

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