Rat extracorporeal circulation model for evaluation of systemic immunotoxicity.
We have applied a rat extracorporeal circulation (EC) model as an evaluation system for the immunotoxicity of medical devices in contact with the blood stream. Combining popular hemodialysis (HD) membranes [a non-biocompatible membrane, Cupurophane (CUP), and more biocompatible membranes, Cu-ammonium rayon (CAR) and polyacrylonitrile (PAN)] with rat EC, we evaluated the elicitation of acute and delayed immunological responses, as well as the effect of repeated EC. Acute effect markers such as the production of tumor necrosis factor (TNF)-alpha and complement activity during EC, and delayed effect markers such as beta2-microglobulin (beta2-M), IgG, and complement 3 levels, were monitored. Acute markers after EC passage showed responses similar to those previously reported in patients with long-term hemodialysis such as TNF-alpha production and increased complement activity. Although beta2-M and IgG levels increased to 3- to 5-fold of the initial concentration within 4 weeks after rat EC, the trend of IgG increase was inversely correlated with membrane biocompatibility (CUP > CAR = PAN), but this did not occur for elevations in beta2-M (PAN > CAR > CUP). These data suggest that this EC model can reproduce similar immunological responses as seen in HD patients, and can be employed to evaluate medical devices and materials for their delayed, systemic, and repeated exposure effects with respect to immunotoxicity.
Adachi
T
T
Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan.
Mogi
M
M
Furuya
M
M
Kojima
K
K
D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity*; D003176:Complement C3 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D004864:Equipment and Supplies / Q000009:adverse effects*; D005069:Evaluation Studies as Topic; D005112:Extracorporeal Circulation; D005260:Female; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008567:Membranes, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis; D018675:Toxicity Tests / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001672:Biocompatible Materials; D003176:Complement C3; D007074:Immunoglobulin G; D008567:Membranes, Artificial; D014409:Tumor Necrosis Factor-alpha