Recombinant human interleukin-1 receptor antagonist protects early myeloid progenitors in a murine model of cyclophosphamide-induced myelotoxicity.

Expression of hematoregulatory cytokines such as interleukin-1 (IL-1) in response to cytotoxic chemotherapy hastens hematopoietic recovery, but may also potentiate myelotoxicity if myeloid progenitors enter cell cycle before drug clearance. In the present study, the ability of recombinant human IL-1 receptor antagonist (IL-1ra) to protect hematopoietic progenitors was studied in a murine model of cyclophosphamide (CPA)-induced myelotoxicity. CF-1 female mice received 200 mg/kg CPA and either 10 mg/kg IL-1ra or an equal volume of 0.05% human serum albumin (HSA) intraperitoneally (i.p.), followed 12 hours later by IL-1ra or HSA. CPA and IL-1ra increased absolute neutrophil counts (ANCs) at days 2 (P = .001) and 14 (P = .0025) after CPA. In IL-1ra-treated mice, colony-forming units granulocyte-macrophage (CFU-GM)/tibia were increased twofold and threefold at days 2 (P = .0047) and 7 (P = .023), respectively, whereas high proliferative potential colony-forming cells (HPP-CFC)/tibia were decreased twofold to threefold at 8 hours (P = .039) and 24 hours (P = .0033), but were approximately threefold higher than HSA-treated mice at day 7 after CPA. Coadministration of CPA and IL-1 enhanced myelotoxicity compared with mice injected with CPA and IL-1ra or HSA. In vivo, IL-1ra protected HPP-CFC, but not CFU-GM, from hydroxyurea suicide after a single dose of CPA, suggesting that IL-1ra inhibited cycling of HPP-CFC. In vitro, IL-1ra did not alter proliferation of CFU-GM, but inhibited IL-1-enhanced proliferation of HPP-CFC. These data suggest that IL-1ra acts as an indirect negative regulator of hematopoiesis and protects HPP-CFC from CPA, possibly by inhibiting IL-1-enhanced proliferation of early myeloid progenitors.

Slow thaw siphon technique for cryoprecipitate production.

The efficacy of the slow thaw siphon technique for making cryoprecipitate was evaluated. A hundred consecutive bags of cryoprecipitate were subjected to analysis. The average Factor VIII:C level in donors plasma was 1.02 IU/ml with slightly lower levels of Factor VIII:C in O group persons and in the older age group. The average Factor VIII:C content per bag of cryoprecipitate was 132 units with the average Factor VIII:C yield of 57.8 per cent. Recovery of the cryoprecipitates made by this method was tested in vivo in ten haemophiliacs with less than 1 per cent activity. An average increment of 1.91 per cent in Factor VIII:C levels was obtained by infusion of 1 IU/kg body weight.