Cellular immune alterations associated with human insulin therapy.
To evaluate the immunogenicity of human insulin preparations, the treatment of 10 insulin-dependent diabetic patients was changed from purified porcine insulins to lente and regular semisynthetic human insulin (SSHI, N = 5) or NPH and regular biosynthetic human insulin (BHI, N = 5). Circulating levels of T lymphocyte subsets, in vitro responses of enriched mononuclear cells to mitogens and circulating insulin antibody measurements were performed before and during the 24 weeks of treatment. Insulin antibody levels did not change significantly in either human insulin treatment group. Circulating levels of Leu 1 and Leu 3 positive cells, identifying total and helper/inducer T lymphocyte populations respectively, and the Leu 3:Leu 2 (helper/inducer: suppressor/cytotoxic) T cell ration were all reduced (p less than 0.025) at eight weeks in the BHI treatment group. Cells identified with murine monoclonal antibody, Leu 7 defining a natural killer cell phenotype, were increased in the SSHI group at four weeks of study (p less than 0.05). There was a decreased pokeweed mitogen-induced proliferation of mononuclear cells in SSHI treated patients (p less than 0.01) at 12 weeks and both insulin treatment groups had increased responses to phytohemagglutinin (p less than 0.05) but not concanavalin A at 24 weeks. These data indicate that changes in the cellular immune system without associated changes in circulating anti-insulin antibody levels can be observed in patients whose treatment was changed from purified porcine to human insulin preparations. Thus, cellular immune responses may be more sensitive than humoral immune responses as indicators of immunological alterations to insulin preparations.
Eichner
H L
HL
Department of Medicine, University of California, Irvine 92717.
Lauritano
A A
AA
Woertz
L L
LL
Selam
J L
JL
Gupta
S
S
Charles
M A
MA
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007328:Insulin / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000032:analysis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology
D007328:Insulin; D007330:Insulin Antibodies