Inhibition of interleukin-2 secretion by factor VIII concentrates: a possible cause of immunosuppression in haemophiliacs.
The inhibitory effect of factor VIII concentrate products on IL-2 secretion by human T-cells was investigated. The six products used widely in the U.K. showed very different activities varying from almost total inhibition to no significant effect. There appeared to be no obvious relationship between inhibitory activity and protein composition but factor VIII itself was not responsible for the effect as affinity purified products were entirely non-inhibitory. The two wet-heated products were most inhibitory whereas dry-heated products were less inhibitory or non-inhibitory. However, a wet-heated version of a non-inhibitory dry-heated product was also non-inhibitory, suggesting that the composition of the concentrate rather than anti-viral treatment is important for immunosuppressive activity. A product treated by the solvent/detergent procedure showed considerable inhibitory activity. Immunoglobulin and albumin products did not inhibit IL-2 secretion to any significant extent, but factor IX concentrates were inhibitory. We suggest that inhibition of IL-2 secretion by factor VIII concentrates may be related to the immunosuppression observed in haemophiliacs treated with high dose factor VIII products and that our results should be considered by clinicians and manufacturers of factor VIII products.
Thorpe
R
R
National Institute for Biological Standards and Control, Potters Bar, Herts.
Dilger
P
P
Dawson
N J
NJ
Barrowcliffe
T W
TW
D000911:Antibodies, Monoclonal; D002460:Cell Line; D005169:Factor VIII / Q000378:metabolism / Q000494:pharmacology*; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D005169:Factor VIII