Host resistance to Trichinella spiralis infection in rats and mice: species-dependent effects of cyclophosphamide exposure

Abstract

Host resistance to Trichinella spiralis infection was compared in male rats (F344) and female mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Doses of CY given to mice were adjusted by body surface area to be comparable to rat doses. Adult parasite elimination was not affected by oral administration of 1.5, 3 or 6 mg CY/kg per day to rats or 1.05, 2.1 or 4.2 mg CY/kg per day to mice for 10 days. In ratsm resistance was suppressed by a single oral dose of 80 mg/kg given the day prior to infection, but was not affected at 20 or 40 mg/kg. A single oral dose of 14, 28 or 56 mg CY/kg did not affect parasite expulsion in mice. Rats were also given four daily intraperitoneal (i.p.) injections of 20, 40 or 80 mg CY/kg per day and mice received 14, 28 or 56 mg CY/kg per day. Infected rats did not survive at the two higher dose levels and parasite expulsion was suppressed at 20 mg/kg per day; parasite expulsion was suppressed in mice by four i.p. injections of 56 mg CY/kg per day, but not by lower doses. In rats, doses of CY which suppressed adult parasite expulsion also severely suppressed the proliferative response of mesenteric lymph node cells (MLNC) to an extract of T. spiralis (TsE). However, significant suppression of TsE-driven blastogenesis occurred at a dose of CY which did not affect parasite expulsion, indicating that the proliferative response in rats was more sensitive to suppression than actual parasite elimination. In contrast, the proliferative response to the T cell mitogen concanavalin A was elevated in the MLNC of CY-exposed rats. This was determined to be related to the interval between CY dosing and the day of assay rather than to an effect of infection with T. spiralis. Mouse MLNC proliferative responses to TsE were not suppressed by CY treatment, even at levels of CY which suppressed adult parasite expulsion. Mice differed from rats in that CY exposure did not affect the proliferative response to concanavalin A in infected animals. The species-dependent differences observed in these studies may have been secondary to the greater sensitivity of rats to CY. Nonetheless, these results highlight the potential for species-specific responses to chemical exposure and underscore the need for additional comparative studies of host resistance in rats and mice.