Selective Inhibition of Thromboxane Biosynthesis in Human Blood Mononuclear Cells and the Effects on Mitogen‐stimulated Lymphocyte Proliferation

Abstract

The effects of six imidazole compounds were examined on thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) production and mitogen‐stimulated lymphocyte transformation in human blood mononuclear cells UK 37248 (4‐(2‐[IH‐imidazol‐l‐yl]ethoxy)benzoic acid), imidazole and 1‐methylimidazole selectively inhibited TxB2 synthesis in a dose‐related manner, with corresponding increases in PGE2 production Clotrimazole, benzimidazole and 2‐methylimidazole preferentially inhibited TxB synthesis but had little effect on PGE2 production Clotrimazole and benzimidazole inhibited proliferative responses of the lymphocytes, but UK 37248 and 1‐methylimidazole did not affect transformation at concentrations which inhibited TxB2 synthesis to a similar level (over 90%) The results do not support involvement of endogenous TxB2 in the process of lymphocyte mitogenesis or in the mechanism of the suppressive effects of some TxB2 synthetase inhibitors.

Blood Changes and Enhanced Thromboxane and 6-Keto Prostaglandin F1α Production in Experimental Acute Plasmodium Bergei Infection in Hamsters

“…O bviously further work in this respect is needed. It is how ever interesting to m ention that som e antimalaria agents, such as mepacrine and chloroquine, possess antiphospholipase activity (20).…”

Immunosuppressive actions of prostaglandins and the possible increase in chronic inflammation after cyclo-oxygenase inhibitors

“…Since inhibitors of thromboxane synthetase activity tend to increase the production of PGE2 and PGI2, they might be expected to increase the inhibition of mitogen-stimulated lymphocyte transformation in mononuclear cell cultures. Gordon et al (1981) [13] examined the effect of 6 imidazole analogues and found that, although all the compounds preferentially inhibited TxB2 production, not all increased PGE2 production. Furthermore, there was no correlation between those which increased PGE2 production by mononuclear cells and inhibition of lymphocyte proliferation.…”

Effects of non-steroidal anti-inflammatory drugs on lymphocyte activation

“…Although thromboxanes are generated by macrophages in comparable quantities to PGE2 [18], evidence for their involvement in lymphocyte activation is less extensive. However, the interpretation of these observations has been questioned, since the capacity of imidazole analogues to affect lymphocyte activation appears unrelated to their capacity to inhibit thromboxane synthetase [24]. However, the interpretation of these observations has been questioned, since the capacity of imidazole analogues to affect lymphocyte activation appears unrelated to their capacity to inhibit thromboxane synthetase [24].…”