Effects of Parathyroid Hormone on Immune Function

Department of Medicine, Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY 10305, USA.
Clinical and Developmental Immunology (Impact Factor: 2.93). 09/2010; 2010(6). DOI: 10.1155/2010/418695
Source: PubMed


Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.

Download full-text


Available from: Claude Bassil, Jul 22, 2014
  • Source
    • "Estrogen (Chighizola and Meroni, 2012) and retinoids (Cassani et al., 2012) also appear to have strong immunomodulatory effects, but like glucocorticoid the implication of VDR regulation as a possible mechanism to modulate immune function has not been investigated. Receptors for the peptide hormone parathyroid hormone (PTH) was recently identified on T cells (Geara et al., 2010). This renders PTH-induced modulation of VDR expression in T cells a possibility as observed for other cell types (Feldman et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The vitamin D receptor (VDR) is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH)2D3, regulates the expression of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH)2D3-VDR signaling on immune function has been the focus of many recent studies as a link between 1,25(OH)2D3 and susceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. It is also becoming increasingly clear that microbes slow down immune reactivity by dysregulating the VDR ultimately to increase their chance of survival. Immune modulatory therapies that enhance VDR expression and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies have been engaged investigating the impact of VDR expression in T cells and found that VDR expression and activity plays an important role in both T cell development, differentiation and effector function. In this review we will analyze current knowledge of VDR regulation and function in T cells and discuss its importance for immune activity.
    Frontiers in Immunology 06/2013; 4:148. DOI:10.3389/fimmu.2013.00148
  • Source
    • "The role of PTH as a potential immune-modulator has been debated. Both B and T lymphocytes express PTH receptors [41].While some studies imply that PTH may be anti-inflammatory [41] other studies found that PTH is in fact increased during MS relapse [42]; still others found no correlation at all between PTH levels and immune cells function [43]. Nevertheless, PTH is a well known stimulator of bone resorption. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines’ levels. In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented. 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed. Vitamin D supplementation to IFN−β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN−β related FLS. Trial registration ClinicalTrials.gov ID: NCT01005095
    BMC Neurology 06/2013; 13(1):60. DOI:10.1186/1471-2377-13-60 · 2.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hemodialysis patients with secondary hyperparathyroidism (SHP) suffer from excessive oxidative stress and inflammation. Vitamin D analogues are currently the first line therapy for SHP, but the influence of vitamin D treatment on inflammation and oxidative stress remains unknown. This study investigated the influence of vitamin D therapy on oxidative stress and inflammatory markers in hemodialysis patients with SHP. Twenty-five patients (mean age 58 ± 12 years, 13 males and 12 females) were enrolled in the study to receive calcitriol treatment for 16 weeks. We evaluated changes in the serum biochemical parameters, inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6) levels], serum oxidative stress condition [total antioxidant status (TAS)], and CD4(+) T-lymphocyte intracellular cytokines [interferon γ (IFN-γ) and interleukin-4 (IL-4)] before and at the end of the 16-week calcitriol treatment. Correlations between each of these factors were also studied. All patients with SHP had low serum 1,25-dihydroxyvitamin D(3) levels and elevated serum levels of intact parathyroid hormone (iPTH), CRP and IL-6. Twenty patients (10 males and 10 females) responded to the calcitriol therapy, with significant decrements in serum iPTH. Our results showed that calcitriol can effectively suppress iPTH secretion, reduce inflammatory markers (CRP and IL-6) and oxidative stress. It can also effectively reduce inflammatory cytokine (CD4(+) IFN-γ) and increase anti-inflammatory cytokine (CD4(+) IL-4). Interestingly, significant correlations between CD4(+) IFN-γ levels and serum iPTH levels, as well as between TAS and iPTH levels were noted. Overall, our study has demonstrated calcitriol treatment significantly attenuates inflammation and oxidative stress in hemodialysis patients with SHP.
    The Tohoku Journal of Experimental Medicine 03/2011; 223(3):153-9. DOI:10.1620/tjem.223.153 · 1.35 Impact Factor
Show more