Cyclophosphamide induces dose- and time-dependent elevations in spleen norepinephrine levels of BALB/c mice

Chemotherapeutic drugs may not only kill rapidly dividing cells but may also alter the extracellular environment of surviving cells. We investigated the possibility that cyclophosphamide might alter the noradrenergic environment of the spleen. Male BALB/cByJ mice were administered a single injection of cyclophosphamide (0, 15, 50, or 100 mg/kg). Seventy-two hours after injection animals receiving 50 or 100 but not 15 mg/kg experienced elevated norepinephrine concentrations (pmol/mg) compared to animals given 0 mg/kg. The time course of changes in norepinephrine concentration was investigated 24-216 h after administration of 50 mg/kg cyclophosphamide; norepinephrine took 48 h to elevate, remained elevated for 48-96 h, and returned to vehicle-treated levels by 120 h. Cyclophosphamide in both experiments reduced spleen mass but did not alter total norepinephrine/spleen. These results suggest that low doses of cyclophosphamide can increase the norepinephrine available to influence cell-cell interactions in the spleen.