Direct effects of HP Acthar Gel® on human B lymphocyte activation in vitro

Nancy Olsen, Dima A. Decker, Paul Higgins, Patrice M. Becker, Carl A. McAloose, Ann L. Benko, William Kovacs

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Both clinical experience and experimental evidence have suggested that Adrenocorticotropic hormone (ACTH) might directly exert immunomodulatory effects not dependent on adrenal steroidogenesis. Methods: The direct effects of H.P. Acthar Gel® (Acthar), a repository preparation containing a porcine ACTH analogue, on human B lymphocyte function were studied in vitro using peripheral blood B cells isolated using anti-CD19 coated magnetic beads and activated by interleukin 4 (IL-4) and CD40 ligand (CD40L). Analysis of expression of messenger RNA (mRNA) encoding activation-induced cytidine deaminase (AICDA) was carried out by quantitative real-time polymerase chain reaction (PCR). Cellular proliferation was assessed by a flow cytometric technique using intracellular staining with carboxyfluorescein succinimidyl ester (CFSE). Immunoglobulin G (IgG) production was measured in cell supernatants using an immunoassay. Results: Acthar was found to exert acute, dose-dependent inhibitory effects on IL-4/CD40L-mediated induction of the expression of activation-induced cytidine deaminase (AICDA) after 24 hours, as well as sustained inhibition of B cell proliferation and IgG production during five more days of culture, without deleterious effects on B cell viability. Conclusions: These experiments demonstrate that Acthar can exert direct effects on the humoral immune system independent of any role in the regulation of adrenal steroidogenesis. Although the impact of these findings on clinical disease was not evaluated in this study, these data support the therapeutic potential of Acthar for the management of autoimmune diseases characterized by B cell activation and aberrant humoral immune function.

Original languageEnglish (US)
Article number300
JournalArthritis Research and Therapy
Volume17
Issue number1
DOIs
StatePublished - Oct 27 2015

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Lymphocyte Activation
Adrenocorticotropic Hormone
B-Lymphocytes
Gels
CD40 Ligand
Interleukin-4
Immunoglobulin G
Cell Proliferation
In Vitro Techniques
Immunoassay
Autoimmune Diseases
Real-Time Polymerase Chain Reaction
Immune System
Blood Cells
Cell Survival
Esters
Swine
Staining and Labeling
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Olsen, Nancy ; Decker, Dima A. ; Higgins, Paul ; Becker, Patrice M. ; McAloose, Carl A. ; Benko, Ann L. ; Kovacs, William. / Direct effects of HP Acthar Gel® on human B lymphocyte activation in vitro. In: Arthritis Research and Therapy. 2015 ; Vol. 17, No. 1.
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Direct effects of HP Acthar Gel® on human B lymphocyte activation in vitro. / Olsen, Nancy; Decker, Dima A.; Higgins, Paul; Becker, Patrice M.; McAloose, Carl A.; Benko, Ann L.; Kovacs, William.

In: Arthritis Research and Therapy, Vol. 17, No. 1, 300, 27.10.2015.

Research output: Contribution to journalArticle

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T1 - Direct effects of HP Acthar Gel® on human B lymphocyte activation in vitro

AU - Olsen, Nancy

AU - Decker, Dima A.

AU - Higgins, Paul

AU - Becker, Patrice M.

AU - McAloose, Carl A.

AU - Benko, Ann L.

AU - Kovacs, William

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