Suppression of endotoxin mitogenicity of spleen cells by lipoxygenase inhibitors and its reversal by 13-hydroxyoctadecadienoic acid.

The effects of several inhibitors of lipoxygenases were investigated in murine spleen cell cultures activated with endotoxin (lipopolysaccharide). It was found that these inhibitors interfere with the proliferative response of the cultures. Indomethacin, a specific cyclooxygenase inhibitor, had no such effect. Endotoxin induced the synthesis of tumour necrosis factor alpha in spleen cells which was prevented by treatment with a lipoxygenase inhibitor. The inhibition of the mitogenic effect of endotoxin could be reversed by addition of 13-hydroxyoctadecadienoic acid. This was not the case with leukotriene B4 and C4 or 15-hydroxyeicosatetraenoic acid. In contrast, these substances had inhibitory effects on the mitogenicity of spleen cells. It is suggested that 13-hydroxyoctadecadienoic acid is involved in the development of the mitogenic reaction, possibly on the level of tumour necrosis factor alpha production of macrophages present in the cultures.