Effects of thymopoietin pentapeptide (TP-5) on in vitro and in vivo IgE production by atopic dermatitis cell subsets.
Atopic dermatitis (AD) patients exhibit multiple immune abnormalities, including T-cell defects that may be partially correctable by the administration of thymic hormones. Our investigations confirmed that peripheral blood mononuclear leukocytes obtained from patients with AD spontaneously synthesized markedly elevated amounts of IgE in vitro. The thymic hormone thymopoietin pentapeptide (TP-5) greatly inhibited this synthesis. An antihuman pan-T cell monoclonal antibody (Lyt3) was used to separate T-cell marker-positive (T+) T cells from marker-negative (T-) B-enriched cells. TP-5 pretreatment of T+ cells resulted in significant reduction of in vitro IgE synthesis by recombined T+ and T- cells, whereas pretreatment of T- B-enriched cells resulted in a nonsignificant reduction in in vitro IgE synthesis. Thus, although pretreatment of both subsets resulted in some degree of reduction, TP-5-induced inhibition of in vitro IgE synthesis was primarily mediated via T cells. The majority of patients' untreated T+ and T4+ cells showed enhanced IgE synthesis, but only one patient's T8+ cells were capable of suppressing IgE synthesis. Thus TP-5 may either induce suppressor T-cell activity or reduce helper T-cell activity. A six-week double-blind clinical trial of TP-5 produced evidence of clinical improvement and alterations of abnormalities of OKT8+ cells, although no significant effects on serum IgE were seen.
D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007962:Leukocytes / Q000145:classification / Q000378:metabolism*; D008211:Lymphocyte Cooperation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism; D016305:Thymopentin; D013946:Thymopoietins / Q000494:pharmacology*; D013951:Thymus Hormones / Q000494:pharmacology*
D000950:Antigens, Ly; D006728:Hormones; D010446:Peptide Fragments; D013946:Thymopoietins; D013951:Thymus Hormones; D007073:Immunoglobulin E; D016305:Thymopentin