Copper(II)(3,5-diisopropylsalicylate)2 accelerates recovery of B and T cell reactivity following irradiation

Abstract

Copper(II)(3,5-diisopropylsalicylate)2 (Cu-DIPS), administered subcutaneously to mice at 80 mg/kg body weight, had marked radioprotective activity. Given 3 h before exposure to 8.0 Gy (800 rad) irradiation, Cu-DIPS increased the 42-day survival from 40% to 86%. Seven days after exposure to 8.0 Gy, there were severe reductions in spleen weight (73%) and cellularity (98%) in both Cu-DIPS- and vehicle-treated mice. Viable spleen cells collected 7 days after irradiation were totally unresponsive to mitogenic or antigenic stimulation regardless of Cu-DIPS or vehicle treatment, suggesting that Cu-DIPS did not prevent radiation-induced damage to mature lymphocytes. At 14 days, when Cu-DIPS-treated mice started to show improved survival over vehicle-treated mice, spleen weights and cellularity were 2.5- and 3.5-fold higher, respectively, in Cu-DIPS-treated mice. Treatment with Cu-DIPS not only enhanced splenic repopulation, but also accelerated the reappearance of both B and T cell reactivities. Spleen cell responsiveness to the B cell mitogen, lipopolysaccharide (LPS), and the T cell mitogen, concanavalin A (Con A), regenerated significantly faster in Cu-DIPS-treated mice. Cu-DIPS also significantly accelerated the regeneration of T-dependent antibody induction. Based on these assays of immunocompetence, Cu-DIPS-treated mice had, on average, a seven-fold greater capacity to respond to immune stimulation than vehicle-treated mice 24 days after irradiation.