Thesis

Host Ingestion of Rapamycin Increased Nematode and Cestode Reproduction

In the push to determine a means to decrease the rate of biological aging in humans, conclusions about over-the-counter use of some anti-aging drugs may be premature. Rapamycin is one drug that, while currently prescribed as an immunosuppressant for various organ transplant recipients, is also being investigated by the National Institutes of Health for over-the-counter use. The presence of intestinal parasites (such as helminths) in the United States is rarely noticed, but intestinal parasitic infections do occur in the United States and citizens of the United States have wide access to over-the-counter drugs. Using rapamycin as an over-the-counter option to combat biological aging, without understanding the effects of rapamycin on susceptibility to parasites, may be deleterious. For my thesis, I examined the effects of rapamycin ingestion by hosts on (1) host susceptibility to two parasite species and (2) on growth and reproduction of the parasites. I found that parasitized hosts food intake, or body mass did not differ between diets, but there was a significant initial increase in body mass and food intake decreased after infection regardless of diet. The rapamycin-fed hosts that were infected with nematodes had a significant decrease in parasite specific immunoglobulin (Ig) G1 when compared to the parasitized hosts on control chow, but for mice infected with the cestode there was no difference in parasite-specific IgG1. Despite changes in IgG1 production, the thymus wet mass, total number of thymus cells, and differential white blood cell counts did not differ for parasitized hosts on rapamycin diet compared to parasitized hosts on control diet. Increase in eosinophil production occurred as expected during nematode infection regardless of diet, but was lessened during cestode infection for rapamycin-fed mice. The infection intensity in the host from either parasite did not differ between diets. The worm length for nematodes did not differ between the host diets, but worms taken from hosts on the rapamycin diet had a significant increase in egg output when compared to worms taken from mice on control chow. Cestodes from hosts on the rapamycin diet had a significant increase in worm mass and egg output when compared to worms taken from mice on the control diet. My pursuit to gain knowledge of the effects of rapamycin on hosts with intestinal parasites has left several questions unanswered, but we have determined that rapamycin ingestion by the host may benefit growth and reproduction of some helminth parasites.

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