The effect of free and carrier-bound cortisol on equine neutrophil function.

This research explores how both free (unbound) and cortisol-binding globulin (CBG)-bound cortisol influence the functioning of neutrophils in the horse’s immune system. In particular, it evaluates how these different types of cortisol might suppress inflammatory responses in both foals and adult horses.

Setting the Context

• Cortisol is a vital hormone in the body that acts against inflammation and increases during bacterial sepsis.
• Traditionally, it was thought that only the unbound, or free, cortisol was biologically active, but recent findings are pointing towards the potential of CBG-bound cortisol in regulating inflammation.
• This study centers its objective on assessing how both free cortisol and CBG-bound cortisol influence the function of equine neutrophils (a type of white blood cells crucial in the immune system) outside of the organism (ex vivo).
• The researchers hypothesized that the presence of CBG would boost the cortisol’s ability to suppress neutrophil’s pro-inflammatory responses.

Methods

• Neutrophils were isolated from 8 foals and 6 adult horses and exposed to Staphylococcus aureus antigen (SAA), a component of a common bacterial pathogen, along with various combinations of hydrocortisone (a form of cortisol), CBG, or both (CBG+HC).
• Then, they recorded and compared the production of inflammatory cytokine (TNF-α, IL-8) and reactive oxygen species (ROS) among the different stimulus and between the different ages with the help of linear mixed-effects models.

Findings

• Results showed that both CBG and CBG+HC were able to restrict ROS production instigated by SAA in the neutrophils of both foals and adult horses, aligning it with levels similar to baseline production.
• However, TNF-α production did not showcase any significant difference between the stimulants.
• When CBG+HC was introduced, it significantly increased IL-8 production by neutrophils in response to SAA in both foals and adults. Interestingly, the response of foals was significantly more pronounced compared to the adults.
• These findings suggest that CBG can directly influence the responses of equine neutrophils. However, the effects are specific to the type of cytokine and the age of the equine.

Implications

• This research provides new insights about cortisol’s complex role in the inflammatory response. Particularly, the findings may help us understand and potentially influence how inflammation is regulated in horses and other animals, considering the contribution of both free and CBG-bound cortisol.
• The study also underscores that age has a significant influence on CBG’s ability to modulate cytokine production. This implies that strategies to regulate inflammation may need to be tailored according to the age of the individual.