EFFECTS OF DRUGS INHIBITING PROSTAGLANDIN OR LEUKOTRIENE BIOSYNTHESISON POSTIRRADIATION HEMATOPOIESIS IN MOUSE

Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), a n inhibitor of prostaglandin production, and esculetin (ESCUL), an inh ibitor of leukotriene production, were tested for their ability to mod ify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated a nd bone marrow-transplanted mice treated with the drugs in the postirr adiation period, stimulatory effects of INDO on CFU-S and GM-CFC popul ations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irra diation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granulocyt es, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. Survival curves for CFU-S an d GM-CFC showed that altered haematopoietic recovery in the INDO- and ESCUL-pretreated mice was not due to changes of intrinsic radiosensiti vity of pluripotent (CFU-S) or committed (GM-CFC) stem cell population s. These results confirm earlier findings suggesting an inhibitory rol e of prostaglandins on haematopoiesis, and provide evidence that endog enous leukotrienes might play a positive role in the regulation of hae matopoietic functions in an irradiated organism.