Adverse reactions to drugs: in vitro studies with isolated cells

Abstract

Objective and design:Drug-induced adverse reactions can be allergic or pseudoallergic in nature, in this study the histamine releasing ability of 4 radiographic contrast media and 2 opioid analgesics was tested on a variety of mast cell containing cell suspensions.

Material:Mast cell containing cell suspensions were obtained from porcine lung, liver, kidneys and heart, as well as rat lung and rat peritoneal lavage.

Treatment:Cells were incubated for 10 min with Angiographin® (amidotrizoate), Hexabrix® (ioxaglate), Rayvist® (ioglycate) or Telebrix® (ioxithalamate) all 10-500 μl/ml or with levomethadone (0.1–5 mM) or pethidine (0–10 mM).

Methods:Histamine was measured using an automated fluorometric method and percentage histamine release calculated.

Results:All agents caused histamine release from porcine cells and rat lung cells. However, rat peritoneal mast cells were refractory to the action of pethidine. Cardiac cells were the most sensitive to the radiographic contrast media but the least sensitive to the opioid analgesics.

Conclusions:The data indicate that mast cells isolated from animal models can provide an indication of those agents likely to induce an adverse pseudoallergic reaction. However, these data should be used together with those obtained from human mast cells, in vivo animal experiments as well as studies using human volunteers and clinical trials as advocated in the Marburg Model.