A comparison of dimaprit, nordimaprit, methylamine and chloroquine as inhibitors of mitogen‐induced lymphocyte activation

Abstract

Methylamine and chloroquine both ‘lysosomotropic’ agents (i.e. agents which sequester in lysosomes) caused a dose‐related inhibition of mitogen‐induced lymphocyte activation in the concentrations which have previously been shown to increase the pH of lysosomes. The dose‐response curves of inhibition of mitogen‐induced lymphocyte activation for chloroquine and methylamine are very steep and are similar to the dose‐response curves obtained with dimaprit and nordimaprit, but very different from the flat dose‐response curves previously described for histamine. Approximate IC50 values were methylamine 6.4 mm, dimaprit 0.13 mm, nordimaprit 0.03 mm and chloroquine 18 μm. It is suggested that the mechanism of action of methylamine and chloroquine may be related to their lysosomotropic action and consequent interference with ligand‐receptor processing, and that dimaprit and nordimaprit but not histamine may act by a similar mechanism.

Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

“…Chloroquine is an antimalarial commonly used as an adjunct agent in SLE maintenance therapy 8 . Inhibition of T lymphocyte mitogenesis was shown in previous studies 39 . However, the current study shows that chloroquine inhibits T lymphocyte proliferation in human whole blood in a concentration‐dependent manner and determines the sensitivity (IC 50 ) of pharmacologic response.…”

“…8 Inhibition of T lymphocyte mitogenesis was shown in previous studies. 39 However, the current study shows that chloroquine inhibits T lymphocyte proliferation in human whole blood in a concentration-dependent manner and determines the sensitivity (IC 50 ) of pharmacologic response. This agent showed no interaction with prednisolone in the present study and displayed an additive effect.…”

Childhood Interstitial Lung Disease

“…It does not bind to DNA by the classic intercalation model, but rather it appears that the small aromatic ring systems can insert between DNA base pairs and induce a bend in the double helix. 102 Chloroquine has been demonstrated to have the following effects: (1) prostaglandin antagonistic effects in the closure of the patent ductus arteriosus and alteration of the biosynthesis of prostaglandins in rabbit peritoneum; 103,104 (2) inhibition of lysosomal enzyme release; 98,105 (3) suppression of the early activation and differentiation of B-cells and therefore suppression of the generation of immunoglobulin secreting cells; 106 (4) inhibition of release of interleukin-1 by monocytes; 107 (5) inhibition of beta-hexosaminidase synthesis and enhancement of excretion of old and newly synthesized enzyme from fibroblasts; 108 (6) significant inhibition of nucleic acid and protein synthesis in rabbit retina; 109 (7) inhibition of membrane phospholipase A 2 of intact neutrophils; 110 and (8) suspected inhibition of fibroblast growth in vitro. 111 When using hydroxychloroquine on patients with CILD, it is often difficult to determine when a sufficient (and effective) dose of medication has been given.…”