Immunostimulatory effects on THP-1 cells by peptide or protein pharmaceuticals associated with injection site reactions.

Abstract

Injection site reaction (ISR) is a common side-effect associated with the use of peptide or protein pharmaceuticals. These types of pharmaceuticals-induced activation of antigen-presenting cells is assumed to be a key step in the pathogenesis of immune-mediated ISR. The present study was designed to evaluate the immunostimulatory properties of peptide or protein pharmaceuticals using human monocytic THP-1 cells. Here, THP-1 cells, with or without phorbol-12-myristate-13-acetate (PMA) pretreatment, were exposed to enfuvirtide and glatiramer acetate (positive controls) or evolocumab (negative control) for 6 or 24 h. PMA treatment differentiated non-adherent monocytic THP-1 (nTHP-1) cells into adherent macrophagic THP-1 (pTHP-1) cells that highly express CD11b and CD36. Enfuvirtide increased the release of cytokines, e.g. TNFα, MIP-1β, and MCP-1, and expression of CD86 and CD54 on nTHP-1 cells at 24 h. Similar immunostimulatory properties of glatiramer acetate were observed both in the nTHP-1 and pTHP-1 cells at 6 h, but the responses were very weak in the pTHP-1 cells. Evolocumab did not affect cytokine secretion or cell surface marker expression in either cell type. Taken together, these in vitro THP-1 cell assays revealed the immunostimulatory properties of enfuvirtide and glatiramer acetate. This assay platform thus could serve as a powerful tool in evaluating potential immune-related ISR risks of peptide or protein pharmaceuticals in humans.

• Authors: Eri Hamamura-Yasuno, Tetsuo Aida, Yoshimi Tsuchiya, Kazuhiko Mori
• Journal: Journal of immunotoxicology (J Immunotoxicol) Vol. 17 Issue 1 Pg. 59-66 (12 2020) ISSN: 1547-6901 [Electronic] England
• PMID: 32091282 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Cytokines
• Enfuvirtide
• Glatiramer Acetate
• evolocumab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, immunology)
• Antigen Presentation (drug effects)
• Antigen-Presenting Cells (drug effects, immunology, metabolism)
• Cytokines (metabolism)
• Drug Evaluation, Preclinical (methods)
• Enfuvirtide (administration & dosage, immunology)
• Glatiramer Acetate (administration & dosage, immunology)
• Humans
• Injection Site Reaction (immunology)
• Injections, Subcutaneous (adverse effects)
• THP-1 Cells