Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure

Gaciong, Zbigniew; Alexiewicz, Jadwiga M.; Linker‐Israeli, Mariana; Shulman, Ira A.; Pitts, Thomas O.; Massry, Shaul G.

doi:10.1038/ki.1991.186

Cited by 53 publications

(31 citation statements)

References 42 publications

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“…Some authors reported B-cell dysfunction and inhibition of Ig production in the presence of PTH in vitro and in vivo [11, 12]. In the present study, we verified that PTX and PTH level normalization stimulated PHA and PWM-induced cell proliferation.…”

Section: Discussionsupporting

confidence: 78%

Restoration of Impaired T-Cell Proliferation after Parathyroidectomy in Hemodialysis Patients

Tzanno-Martins¹,

Futata²,

Jorgetti

et al. 2000

Nephron

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Background/Aims: Severe secondary hyperparathyroidism is not infrequent in hemodialysis patients and recent studies suggest that parathyroid hormone (PTH) may play a role in the genesis of cell immunity abnormalities in uremia. The aim of the present study is to describe the effect of parathyroidectomy on T- and B-cell functions in hemodialysis patients. Methods: The study was performed on 6 patients with severe secondary hyperparathyroidism. iPTH, B, CD4⁺, CD8⁺, total number of lymphocytes, lymphoproliferative response to PHA, PWM and Candidin, and IgG, IgM, IL-2 production in vitro were determined 1 day before and 4 months after parathyroidectomy. Results: The lymphoproliferative response to PHA increased significantly after parathyroidectomy. We also observed a trend to an increase in production of IgG and IgM after PWM stimulation before therapy. Conclusion: The present study suggests that patients with extremely high levels of PTH show a complete restoration of impaired T-cell proliferation after parathyroidectomy.

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Section: Discussionsupporting

confidence: 78%

Restoration of Impaired T-Cell Proliferation after Parathyroidectomy in Hemodialysis Patients

Tzanno-Martins¹,

Futata²,

Jorgetti

et al. 2000

Nephron

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“…Exogenous PTH blocks the effect of mitogens on immu noglobulin production by B cells obtained from normal subjects in vitro, but has no effect on mitogen-stimulated immunoglobu lin production by B cells isolated from CRF patients, suggesting that their B cells have been maximally suppressed by PTH in vivo. Consistent with this hypothesis is the observa tion that intracellular calcium is greater in B cells obtained from dialysis patients [28]. In addition, the percent inhibition of mitogenstimulated B-cell proliferation is inversely proportional to serum PTH levels in B cells isolated from dialysis patients [27], also sup porting this hypothesis.…”

Section: Immunoglobulinsupporting

confidence: 69%

Derangements of Protein Metabolism in Chronic Renal Failure

Kaysen¹,

Rathore²

1996

Blood Purif

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The principal physiologic roles of the kidney are to maintain normal plasma volume and composition, to regulate calcium metabolism by controlling the synthesis of 1,25-dihydroxy-cholycalciferol (1,25-D₃), to regulate hematocrit and to metabolize low molecular weight peptides. Alterations in protein metabolism result principally from losses of these functions. Metabolic acidosis causes increased skeletal muscle protein catabolism through regulated activation of the ATP-ubiquitin-proteasome proteolytic pathway. Increased proteolysis is followed by oxidation of branch chain essential amino acids. Alanine and glycine released from muscle and glutamine and glu-tamate released from liver serve as substrate for renal ammoniagenesis, ultimately correcting acidosis. The cycle is subverted when kidneys are absent. Secretion of a variety of proteins is also perturbed. Hepatic secretion of insulin like growth factor-1 (IGF-I) in response to growth hormone is reduced. This in turn contributes to growth retardation, adding to the effects of acidosis. Muscle is also resistant to insulin in renal failure. Renal production of 1,25-D₃ is reduced contributing to hyperparathyroidism, which in turn causes increased intracellular calcium in a variety of tissues contributing to decreased synthesis of immunoglobulins, mitogen-stimulated T-cell proliferation, and decreased glucose-stimulated insulin secretion. Hepatic synthesis of some proteins, such as apolipo-protein A-I and IGF-I are decreased, but synthesis of others, such as albumin, is normal. Low molecular weight peptides such as β₂-microglobulin, normally filtered and catabolized in the proximal tubule, accumulate in plasma and may have deleterious effects.

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“…Patients with renal failure-related hyperparathyroidism have impaired humoral immunity, including reduced B cell proliferation and antibody production [43]. Lymphocytes have receptors for PTH [44], and it has been reported that PTH inhibits production of IgG, IgA and IgM by cultured human B cells, while the inactivation of PTH abolishes this inhibitory effect [45]. The respective contributions of these various mechanisms to immune dysfunction in patients with hyperparathyroidism need to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 production and secretion by human parathyroids

Safley¹,

Villinger

Jackson³

et al. 2004

Clinical and Experimental Immunology

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SUMMARYParathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.

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Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure

Cited by 53 publications

References 42 publications

Restoration of Impaired T-Cell Proliferation after Parathyroidectomy in Hemodialysis Patients

Restoration of Impaired T-Cell Proliferation after Parathyroidectomy in Hemodialysis Patients

Derangements of Protein Metabolism in Chronic Renal Failure

Interleukin-6 production and secretion by human parathyroids

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