The Effect of Anthelmintics on Proinflammatory Cytokine Responses in Treated Horses

Cyathostomes (small strongyles) are intestinal parasitic worms of horses.  Cyathostome infections can usually be controlled with anthelmintics, but sometimes treatment can also be associated with ulcers and acute inflammation in the intestinal tissues. This inflammation likely represents the host response to degenerating parasites in the tissues. Since different classes of anthelmintics have unique mechanisms of action, we hypothesize that they will also exhibit characteristic pro-inflammatory tendencies.  To test this hypothesis, we treated ponies with three different classes of anthelmintics: benzimidazoles (fenbendazole), tetrahydropyrimidines (pyrantel tartrate), and macrocyclic lactones (moxidectin), and monitored the expression of inflammatory genes post-treatment.  Peripheral blood samples were collected daily for 2 weeks, and quantitative real-time PCR was utilized to determine pro-inflammatory gene expression post-treatment.  Fecal egg counts were used to evaluate the efficacy of each drug. Ponies treated with fenbendazole showed evidence of augmented inflammatory gene expression and reduced egg counts significantly up to 14 days post-treatment. While treatment with pyrantel tartrate significantly reduced fecal egg counts consistently throughout the study and weeks thereafter, it also elicited a pro-inflammatory response, though not as pronounced as that seen with fenbendazole treatment. Treatment with moxidectin, however, showed no signs of increased inflammatory gene expression and was the most successful in reducing fecal egg counts.   As expected, the inflammatory response was related to the class of anthelmintic.  The significance of this inflammatory response remains unclear at this time.