Alan D. Perris

Interleukin 2 stimulates T cell proliferation using a calcium flux

A preparation enriched in rat interleukin 2 caused enhanced DNA synthesis in an interleukin 2-dependent mouse cytotoxic T cell line, in lectin transformed mouse splenocytes and in rat thymocytes. The enhanced proliferation due to interleukin 2 could be abrogated by chelating calcium from the culture medium or blocking calcium entry into the cells. Compounds which interfere with the function of calmodulin also inhibited proliferation. The addition of interleukin 2 to IL-2 dependent cells caused an increase in the intracellular concentration of calcium ions, as measured using Quin 2. The requirement for IL-2 by blasts and thymocytes could be replaced by calcium ionophore. The results implicate a calcium flux as an essential component of the action of interleukin 2 on its target cells.

Studies on the Inhibitory Effects of Analogues of Dapsone on Neutrophil Function In-vitro*

We have compared twelve sulphone analogues of dapsone in terms of inhibition both of zymosan‐mediated human neutrophil respiratory burst and inhibition of interleukin‐1‐stimulated neutrophil adhesion to transformed human umbilical vein endothelial cells.

The promotion of mitosis in cultured thymic lymphocytes by acetylcholine and catecholamines.

Thymic lymphoblasts possess beta-adrenergic, dopaminergic and nicotinic receptors. When activated by high concentrations of adrenaline, isoprenaline, dopamine and acetylcholine, magnesium-dependent events are initiated, which culminate in mitosis. These events can be blocked by testosterone. The cells also possess muscarinic and alpha-adrenergic receptors which respond to low concentrations of acetylcholine, carbamylcholine and noradrenaline. In these cases calcium-dependent, oestradiol-blockable mechanisms are triggered which eventually lead to cell division.

Preliminary evaluation of the toxicity and efficacy of novel 2,4-diamino-5-benzylpyrimidine-sulphone derivatives using rat and human tissues in vitro

Four novel combined dapsone and trimethoprim analogues, K-120, K-150, K-138 and DRS-506, have been compared with dapsone in their methaemoglobin forming abilities as well as their anti-inflammatory properties using rat and human tissues in vitro. All four compounds formed consistently less methaemoglobin compared with dapsone in both the rat and human microsomes. Using human microsomes from five livers, K-120 was significantly less toxic than the other analogues in three of the five livers (P < 0.01). DRS-506 and K-138 both inhibited the human neutrophil respiratory burst to a significantly greater degree compared with dapsone at 0.5 mM (P < 0.01), while K-120 and K-150 showed no significant effect at 0.5 mM. At 1 mM, DRS-506, K-120 and K-138 were more potent than dapsone (P < 0.01), although K-150 appeared to increase the neutrophil activation. All four analogues caused a significant reduction in neutrophil adhesion to human umbilical vein cells at 0.1 mM. In view of its efficacy and low toxicity, K-120 shows considerable promise for future clinical evaluation.