Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis

E. Mocchegiani, M. Provinciali, G. Di Stefano, A. Nobilini, G. Caramia, L. Santarelli, A. Tibaldi, N. Fabris

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P <0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P <0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of α2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P <0.01) and between zinc or active thymulin and NK activity (r = 0.70, P <0.01 and r = 0.88, P <0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.

Original languageEnglish
Pages (from-to)214-224
Number of pages11
JournalClinical Immunology and Immunopathology
Volume75
Issue number3
DOIs
Publication statusPublished - 1995

Fingerprint

Circulating Thymic Factor
Cystic Fibrosis
Biological Availability
Zinc
Thymus Hormones
Interleukin-2
Cellular Immunity
Natural Killer Cells
Macroglobulins
T-Lymphocyte Subsets
Growth
Infection
Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

Cite this

Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis. / Mocchegiani, E.; Provinciali, M.; Di Stefano, G.; Nobilini, A.; Caramia, G.; Santarelli, L.; Tibaldi, A.; Fabris, N.

In: Clinical Immunology and Immunopathology, Vol. 75, No. 3, 1995, p. 214-224.

Research output: Contribution to journalArticle

Mocchegiani, E. ; Provinciali, M. ; Di Stefano, G. ; Nobilini, A. ; Caramia, G. ; Santarelli, L. ; Tibaldi, A. ; Fabris, N. / Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis. In: Clinical Immunology and Immunopathology. 1995 ; Vol. 75, No. 3. pp. 214-224.
@article{1cbc489538fb4648bbfe77ca72b6b403,
title = "Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis",
abstract = "An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P <0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P <0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of α2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P <0.01) and between zinc or active thymulin and NK activity (r = 0.70, P <0.01 and r = 0.88, P <0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.",
author = "E. Mocchegiani and M. Provinciali and {Di Stefano}, G. and A. Nobilini and G. Caramia and L. Santarelli and A. Tibaldi and N. Fabris",
year = "1995",
doi = "10.1006/clin.1995.1074",
language = "English",
volume = "75",
pages = "214--224",
journal = "Clinical Immunology and Immunopathology",
issn = "0090-1229",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis

AU - Mocchegiani, E.

AU - Provinciali, M.

AU - Di Stefano, G.

AU - Nobilini, A.

AU - Caramia, G.

AU - Santarelli, L.

AU - Tibaldi, A.

AU - Fabris, N.

PY - 1995

Y1 - 1995

N2 - An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P <0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P <0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of α2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P <0.01) and between zinc or active thymulin and NK activity (r = 0.70, P <0.01 and r = 0.88, P <0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.

AB - An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P <0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P <0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of α2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P <0.01) and between zinc or active thymulin and NK activity (r = 0.70, P <0.01 and r = 0.88, P <0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.

UR - http://www.scopus.com/inward/record.url?scp=0029034230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029034230&partnerID=8YFLogxK

U2 - 10.1006/clin.1995.1074

DO - 10.1006/clin.1995.1074

M3 - Article

C2 - 7539347

AN - SCOPUS:0029034230

VL - 75

SP - 214

EP - 224

JO - Clinical Immunology and Immunopathology

JF - Clinical Immunology and Immunopathology

SN - 0090-1229

IS - 3

ER -