Conflict of interest statement
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MISP) (No. 2013R1A4A1069486).
Cyathostomin (small strongyle) parasites are ubiquitous in grazing horses world-wide and control programs are typically based on anthelmintic treatments applied routinely year-round with the objective being to avoid large burdens that can constitute a threat to equine health (Lloyd et al., 2000; O’Meara and Mulcahy, 2002; Earle et al., 2002).
Strongyle type parasites appear to have complex interaction with the immune system. In horses, experimental inoculation with cyathostomins and Strongylus vulgaris evoke a subtle acute phase inflammatory response (Andersen et al., 2014), and the number of mucosal larvae has been shown to correlate with large intestinal mucosal expression of the pro-inflammatory interleukin (IL-4) as well as the regulatory and anti-inflammatory cytokine IL-10 (Davidson et al., 2005). In human medicine it has become well-established that helminth infections can relieve the symptoms of inflammatory disorders such as melatonin receptor agonist (Araujo et al., 2004) and chronic inflammatory bowel syndrome (Crohn\’s disease) (Cooper, 2004; McKay, 2009), probably through parasitic stimulation of a release of the regulatory and anti-inflammatory IL-10 (McKay, 2009).
A number of studies have documented that anthelmintic treatment can evoke a systemic inflammatory response, and that the extent of this response is associated with the anthelmintic drug class used (Steinbach et al., 2006; Nielsen et al., 2013; Betancourt et al., 2014). When very pronounced, this inflammation can be part of the parasitic disease complex called larval cyathostominosis (Reid et al., 1995), which is characterized by mass emergence of large numbers of encysted larvae from the mucosal walls of the large intestine. To add to the complexity of this inflammatory response following anthelmintic treatment, a recent study with a murine asthma model suggested that ivermectin might have anti-inflammatory effects (Yan et al., 2011). To our knowledge this has not yet been investigated in any type of non-rodent mammals, but the observation is supported by equine studies reporting little or no signs of inflammatory reaction following treatment with moxidectin, which like ivermectin belongs to the macrocyclic lactone drug class (Steinbach et al., 2006; Nielsen et al., 2013; Betancourt et al., 2014).
Vaccination is another commonly applied practice in equine management, and the response to a vaccine is largely consists of both inflammatory and immunologic reactions. The acute phase inflammatory response was recently characterized in response to two commercially available equine influenza/tetanus vaccines: an inactivated influenza/tetanus toxoid Immune Stimulating COMplex (ISCOM) vaccine and an adjuvanted, live recombinant vector vaccine (Andersen et al., 2011). The study revealed a prominent acute phase response to both vaccines during the first 96h after vaccination, but with the response being more pronounced following administration of the ISCOM vaccine. Given the information presented above, there is reason to hypothesize that administration of an anthelmintic may interfere with (a) the inflammatory reaction to the vaccination and (b) the immune response to that vaccine. For convenience, horses are likely to often receive vaccinations and anthelmintics at the same time. A previous study suggested a possible interaction between gastrointestinal worm burdens and the immune response to antigen stimulation in ponies (Edmonds et al., 2001), and a recent study performed in cattle documented a beneficial effect of deworming calves two weeks prior or at the day of vaccination with a combination vaccine against respiratory viruses (Schutz et al., 2012).
Materials and methods