Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency
ObjectiveThe primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HS...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489254/full |
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| author | Laura Tomasello Antonina Coppola Giuseppe Pizzolanti Giuseppe Pizzolanti Carla Giordano Giorgio Arnaldi Valentina Guarnotta |
| author_facet | Laura Tomasello Antonina Coppola Giuseppe Pizzolanti Giuseppe Pizzolanti Carla Giordano Giorgio Arnaldi Valentina Guarnotta |
| author_sort | Laura Tomasello |
| collection | DOAJ |
| description | ObjectiveThe primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.MethodsWe prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. Serum inflammatory parameters and peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and after 12 months of treatment.ResultAt baseline, significantly higher CD4+ and CD8+ (both p < 0.001) T-cell percentages, a lower CD4+/CD8+ ratio (p < 0.05), and higher CD25+ and CD4+/CD25+ T cells (both p < 0.001) were observed in PAI compared to controls. After 12 months of DR-HC treatment, we found significantly lower IL-6 (p = 0.019), IL-17A (p = 0.046), COX-2 (p < 0.001), HSP-70 (p = 0.006), and TXN-1 (p = 0.008) and higher PD-L1 (p < 0.001) and IDO (p < 0.001) mRNA values compared to baseline. After 12 months of DR-HC treatment, a significant increase in CD4+ T cells (p = 0.012), PD-L1 (p = 0.003), and IDO (p < 0.001) and a decrease in CD8+ T cells (p < 0.001), IL-6 (p = 0.003), IL-17A (p = 0.0014), COX-2 (p < 0.001), HSP-70 (p = 0.005), and TXN-1 (p = 0.0008), as well as a significantly higher conversion in the CD4+/CD8+ ratio (p = 0.033), were observed compared to conventional GCs.ConclusionsThe switch from conventional GCs to DR-HC treatment altered the T lymphocyte phenotype and CD4+/CD8+ ratio in a Treg-independent manner, inducing significant improvements in the immune and inflammatory profile in PAI. |
| format | Article |
| id | doaj-art-8bb9444c9df046798d5ef6a2cdfa0eec |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-8bb9444c9df046798d5ef6a2cdfa0eec2025-01-23T06:56:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14892541489254Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiencyLaura Tomasello0Antonina Coppola1Giuseppe Pizzolanti2Giuseppe Pizzolanti3Carla Giordano4Giorgio Arnaldi5Valentina Guarnotta6Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyAdvanced Technologies Network Center (ATEN Center), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, ItalyObjectiveThe primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.MethodsWe prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. Serum inflammatory parameters and peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and after 12 months of treatment.ResultAt baseline, significantly higher CD4+ and CD8+ (both p < 0.001) T-cell percentages, a lower CD4+/CD8+ ratio (p < 0.05), and higher CD25+ and CD4+/CD25+ T cells (both p < 0.001) were observed in PAI compared to controls. After 12 months of DR-HC treatment, we found significantly lower IL-6 (p = 0.019), IL-17A (p = 0.046), COX-2 (p < 0.001), HSP-70 (p = 0.006), and TXN-1 (p = 0.008) and higher PD-L1 (p < 0.001) and IDO (p < 0.001) mRNA values compared to baseline. After 12 months of DR-HC treatment, a significant increase in CD4+ T cells (p = 0.012), PD-L1 (p = 0.003), and IDO (p < 0.001) and a decrease in CD8+ T cells (p < 0.001), IL-6 (p = 0.003), IL-17A (p = 0.0014), COX-2 (p < 0.001), HSP-70 (p = 0.005), and TXN-1 (p = 0.0008), as well as a significantly higher conversion in the CD4+/CD8+ ratio (p = 0.033), were observed compared to conventional GCs.ConclusionsThe switch from conventional GCs to DR-HC treatment altered the T lymphocyte phenotype and CD4+/CD8+ ratio in a Treg-independent manner, inducing significant improvements in the immune and inflammatory profile in PAI.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489254/fullregulatory T-lymphocytesinterleukin-6PD-L1HSP-70CD4 +/CD8 + ratioAddison’s disease |
| spellingShingle | Laura Tomasello Antonina Coppola Giuseppe Pizzolanti Giuseppe Pizzolanti Carla Giordano Giorgio Arnaldi Valentina Guarnotta Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency Frontiers in Immunology regulatory T-lymphocytes interleukin-6 PD-L1 HSP-70 CD4 +/CD8 + ratio Addison’s disease |
| title | Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| title_full | Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| title_fullStr | Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| title_full_unstemmed | Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| title_short | Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| title_sort | dual release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency |
| topic | regulatory T-lymphocytes interleukin-6 PD-L1 HSP-70 CD4 +/CD8 + ratio Addison’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489254/full |
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