Effect of cyclophosphamide pretreatment on autoimmune encephalomyelitis in rats

Abstract

We studied the effect of a low dose cyclophosphamide (CY) treatment on the clinical course of experimental autoimmune encephalomyelitis (EAE) in rats from three resistant or low-susceptible strains: Fischer, Brown-Norway, PVG, and the F₁ hybrid between the two former strains. Treatment with 40 mg/kg two days before immunization resulted in a marked potentiation of EAE development in Fischer and PVG rats, but not in BN rats or F₁(BN x F) hybrids. The effect of the CY treatment was a short period of severe lymphoid cell depletion with an increase in the quotient between T cells reacting with w3/25 monoclonal antiserum and such reacting with ox-8 antiserum, indicating a relative reduction in suppressor/cytotoxic cell counts. Treatment of Fischer or PVG rats, after CY treatment, for five days with thymic hormone factor (THF) normalized T cell ratios and restored the rats to a state of low susceptibility. It is concluded that Fischer and PVG rats have an EAE suppressive mechanism dependent on CY-sensitive suppressor lymphocytes, while there may be other mechanisms of resistance to EAE in BN rats.