Conditioned immunosuppressive effect of cyclophosphamide on delayed-type hypersensitivity response and a preliminary analysis of its mechanism

In the present study, camphor odor and intraperitoneal (i.p.) injection of cyclophosphamide (CY) were used as conditioned stimulus (CS) and unconditio ned stimulus (US), respectively. In the unconditioned group, mice were expo sed to camphor odor for 1 h followed by an i.p. injection of CY (75 mg/kg). On the next day, the above CS/US association trial session was repeated fo llowed by smearing dinitrochlorobenzene (DNCB) on mouse abdominal skin for sensitizing the animal for delayed-type hypersensitivity (DTH) response. Fi ve days after DNCB sensitization, mice were exposed to camphor odor(1 h), f ollowed by an i.p. injection of CY, and then DNCB was smeared on the left e ar of mice for the challenge of DTH response. Both the left/right ear weigh t ratio and the activity of leukocyte migration inhibitory factor (LMIF) we re used as the index of DTH response, which was done 24 h after DNCB challe nge. In the conditioned group, the treatment was the same as that in the un conditioned group, except that normal saline was injected on day 5 instead of CV. Furthermore, in order to analyze the mechanism of the conditioned re sponse (CR), the mouse serum from the conditioned group (CR serum) was inje cted into normal mice 6 h prior to DNCB challenge. Results showed that in t he conditioned group, left/right ear weight ratio and LMIF activity were st atistically lower than that in the DTH group, and there was no difference b etween conditioned and unconditioned groups. Thus, an animal model of condi tioned immunosuppressive response had been established. The results also sh owed that after CR serum was injected into normal mice, DTH response was al so significantly suppressed. However, if CR serum was treated with dialysis (10,000 molecular weight cut-off), the suppressive effect of CR serum on D TH response disappeared. Taken together, the data suggested that a chemical compound(s) in serum, with a molecular weight less than 10,000, was import ant in mediating the conditioned immunosuppressive response. This may be a very important molecule(s) that could be very critical to our understanding of the interaction between the central nervous system and immune function. Copyright (C) 2000 S. Karger AG, Basel.