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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1489254

Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cells inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency

Provisionally accepted
Laura Tomasello Laura Tomasello 1Antonina Coppola Antonina Coppola 1Giuseppe Pizzolanti Giuseppe Pizzolanti 1,2*Carla Giordano Carla Giordano 1Giorgio Arnaldi Giorgio Arnaldi 1Valentina Guarnotta Valentina Guarnotta 1
  • 1 Dipartimento di Promozione della Salute, Medicina Materno-Infantile, Interna e Specialistica di Eccellenza G. D'Alessandro, Università degli Studi di Palermo, Palermo, Sicily, Italy
  • 2 Advanced Technologies Network Center, University of Palermo, Palermo, Sicily, Italy

The final, formatted version of the article will be published soon.

    Objective: The 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 deathligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.We 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.Results: At 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.The 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.

    Keywords: Regulatory T-lymphocytes, Interleukin-6, PD-L1, HSP-70, CD4 + /CD8 + ratio, Addison's disease, Flow Cytometry

    Received: 31 Aug 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Tomasello, Coppola, Pizzolanti, Giordano, Arnaldi and Guarnotta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Giuseppe Pizzolanti, Dipartimento di Promozione della Salute, Medicina Materno-Infantile, Interna e Specialistica di Eccellenza G. D'Alessandro, Università degli Studi di Palermo, Palermo, 90127, Sicily, Italy

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