In vitro effects of the toll-like receptor agonists monophosphoryl lipid A and CpG-rich oligonucleotides on cytokine production by equine cells.

This research investigates the application of two ‘Toll-Like Receptor’ (TLR) agonists to improve allergic disease treatment in horses, with focus on Insect Bite Hypersensitivity (IBH). The study suggests that the TLR-agonist monophosphoryl lipid A (MPLA) could be a good candidate for improving allergy vaccines, whilst CpG-rich oligodeoxynucleotides (CpG-ODN) could aid in treatment of infectious or neoplastic diseases in horses.

Context and Purpose of the Study

• For horses, IBH is an allergic reaction to antigens from Culicoides spp. While allergen-specific immunotherapy (AIT) has often been used as a source of treatment with allergies, for IBH it has not yielded successful results.
• The TLR agonists have the potential to shift the immune response from an allergy-promoting state (Th2) to a regulatory response (Th1). The researchers aimed to assess two immunomodulatory TLR Agonists – monophosphoryl lipid A (MPLA) and CpG-rich oligodeoxynucleotides (CpG-ODN) – in vitro, as potential vaccine additives to make AIT more successful for treating IBH.

Methodology of the Research

• Peripheral blood mononuclear cells (PBMCs) were collected from healthy horses and those affected by IBH. They were stimulated with either MPLA or CpG-ODN, with or without Culicoides spp. allergens present.
• The concentration of cytokines – interferon (IFN)-α, IFN-γ, interleukin (IL)-4, IL-10, and IL-17 – was measured in the stimulated PBMCs’ supernatants. These cytokines play different roles in the immune response, some promoting inflammation, while others promote an immune response or regulate the immune system.

Findings of the Research

• MPLA stimulated the secretion of IL-10 in all horses, irrespective of the type and presence of antigens. In addition, it dampened the antigen-induced production of IFN-γ, IL-4, and IL-17. This indicates a shift towards a regulatory immune response and away from an allergy-promoting response.
• CpG-ODN increased the production of IFN-α, IFN-γ, and IL-4 but had little effect on IL-10 production. This means it may have a role in treatment strategies for infectious or neoplastic diseases, where increased activation of the immune response might be beneficial.

Research Implications

• The research implies that MPLA holds promise as an additive for allergy vaccines in horses. By promoting a regulatory immune response, it may help to modulate the allergic reaction experienced by horses with IBH.
• CpG-ODN might not be suitable as an emphasizer for AIT due to its lack of effect on IL-10 production, but its effect on IFN-γ and IFN-α suggests potential use in combination with vaccines for treating infectious or neoplastic horse diseases.