Neutrophilic bronchiolitis is the primary lesion in asthma-affected horses. Neutrophils are key actors in host defense, migrating toward sites of inflammation and infection, where they act as early responder cells toward external insults. However, neutrophils can also mediate tissue damage in various non-infectious inflammatory processes. Within the airways, these cells likely contribute to bronchoconstriction, mucus hypersecretion, and pulmonary remodeling by releasing pro-inflammatory mediators, including the cytokines interleukin (IL)-8 and IL-17, neutrophil elastase, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). The mechanisms that regulate neutrophil functions in the tissues are complex and incompletely understood. Therefore, the inflammatory activity of neutrophils must be regulated with exquisite precision and timing, a task achieved through a complex network of mechanisms that regulates neutrophil survival. The discovery and development of compounds that can help regulate ROS, NET formation, cytokine release, and clearance would be highly beneficial in the design of therapies for this disease in horses. In this review, neutrophil functions during inflammation will be discussed followed by a discussion of their contribution to airway tissue injury in equine asthma.

Accumulating evidence indicates that, analogous to n-6 PUFA, n-3 PUFA are enzymatically converted into diverse families of bioactive mediators that play numerous roles in physiology. These mediators, which include the resolvins, protectins and maresins, are particularly important in resolving acute inflammation and also appear to play a role in enhancing host defence. Given the protective actions of n-3 PUFA in human subjects and in animal models of disease, active generation of bioactive mediators may in part underlie these protective effects. Several studies have demonstrated that bioactive autacoids generated from n-3 PUFA have direct anti-inflammatory and pro-resolution actions, and the structures of many of these endogenous mediators have been elucidated. The diverse roles of these lipid mediators in health and disease, regulation of their biosynthesis, as well as identification of specific receptors and cellular targets, are emerging. This brief review will highlight the biosynthesis of resolvins, protectins and maresins, and discuss their receptor-mediated biological actions in promoting the resolution of inflammation. Their potential use as a new class of pro-resolution therapeutics, as well as gaps in knowledge and challenges for future research, will also be discussed. Overall, the identification of these novel families of lipid mediators has yielded insight into the protective actions of n-3 PUFA and may lead to the development of an entirely new class of therapeutics aimed at regulating inflammation and host defence.

Both fish oil (FO) and curcumin have potential as anti-tumour and anti-inflammatory agents. To further explore their combined effects on dextran sodium sulphate (DSS)-induced colitis, C57BL/6 mice were randomised to four diets (2 × 2 design) differing in fatty acid content with or without curcumin supplementation (FO, FO+2 % curcumin, maize oil (control, MO) or MO+2 % curcumin). Mice were exposed to one or two cycles of DSS in the drinking-water to induce either acute or chronic intestinal inflammation, respectively. FO-fed mice exposed to the single-cycle DSS treatment exhibited the highest mortality (40 %, seventeen of forty-three) compared with MO with the lowest mortality (3 %, one of twenty-nine) (P = 0·0008). Addition of curcumin to MO increased (P = 0·003) mortality to 37 % compared with the control. Consistent with animal survival data, following the one- or two-cycle DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared with MO. In contrast, compared with other diets, combined FO and curcumin feeding enhanced the resolution of chronic inflammation and suppressed (P < 0·05) a key inflammatory mediator, NF-κB, in the colon mucosa. Mucosal microarray analysis revealed that dietary FO, curcumin and FO plus curcumin combination differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.