Interactions between non-steroidal anti-inflammatory drugs and biological membranes—II: Swelling and membrane permeability changes induced in some immunocompetent cells by various non-steroidal anti-inflammatory drugs

Abstract

Non-steroidal anti-inflammatory drugs (NSAID) that are known to induce pseudo-energized high-amplitude swelling of mitochondrial preparations also induce swelling in various types of lymphocytes, namely: rat and rabbit thymocytes, rat and rabbit lymph node cells, and human and rat circulating lymphocytes obtained by thoracic duct drainage. The swelling of these immunocompetent cells was measured by light scattering. With the important exception of gold salts (no effect) and salicylates (very poor activity), almost all the NSAID that we have studied were able to induce cell swelling in vitro, but only at relatively high concentrations of these drugs compared to the concentrations which induced mitochondrial swelling (liver, kidney). The most dramatic effect was observed with N-arylanthranilates (fenamates), especially with flufenamic acid, which was used to study the mechanism of this drug action. The magnitude of the swelling is poorly related to the concentration of the drug, but the rapidity of this phenomenon seems to be a concentration-related phenomenon. If p-chloromer-curibenzoate ( p-CMB) or Mersalyl is present in the medium, the rate of NSAID-induced swelling is enhanced and appreciable cell swelling can even be demonstrated for drugs which otherwise (i.e. without p-CMB or Mersalyl) cause little cell swelling, e.g. phenylbutazone. By contrast, iodacetamide and N-ethylmaleimide fail to enhance the swelling. These activities seem to be related both to reactions with membrane thiol groups and modifications of the membrane charges by these compounds. The ionic composition of the medium is critical for this swelling activity and a cationic as well as an anionic selectivity was found for this phenomenon. These results suggest that one possible effect of the NSAID on leukocytes implicated in the immune and inflammatory responses may be on the permeability of the cell membrane to various ions.