Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) Reduces Allergic Inflammation of Ovalbumin-Sensitized Mice

Am J Rhinol Allergy. 2022 Jul;36(4):432-439. doi: 10.1177/19458924211072364. Epub 2022 Jan 7.

Abstract

Background: Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug.

Objectives: We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model.

Methods: We divided 40 four-week-old BALB/c mice into four groups: control group (n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis.

Results: Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group.

Conclusions: Aba suppresses allergic inflammation and appears to be a good treatment for AR.

Keywords: BALB/c mice; CD28; CD4; CTLA4-Fc; Th2 cells; abatacept; allergy; inflammation; ovalbumin; rhinitis.

MeSH terms

  • Abatacept / metabolism
  • Abatacept / therapeutic use
  • Animals
  • CTLA-4 Antigen / metabolism
  • CTLA-4 Antigen / therapeutic use
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunoglobulin E / metabolism
  • Inflammation* / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nasal Mucosa / metabolism
  • Ovalbumin
  • Rhinitis, Allergic* / drug therapy
  • Rhinitis, Allergic* / metabolism

Substances

  • Abatacept
  • Ovalbumin
  • CTLA-4 Antigen
  • Cytokines
  • Immunoglobulin E