Normalization of immunoregulatory T-helper T-suppressor sublineages and cell-mediated immunity by isoprinosine in vitro in the early stages of AIDS.
Applying flow cytometric analysis and a panel of monoclonal antibodies that define functional subsets and stages of lymphocyte differentiation, we found both inducer and suppressor regulating subsets of helper T cells to be depressed with concurrent increase in the functionally active effector suppressor T cells in prodromal homosexuals and patients with AIDS. Concomitantly a broad spectrum of aberrations in all stages of B cell developments were observed. Failure of isolated peripheral blood lymphocytes from these subjects to respond to formalin-fixed Staphylococcus aureus cowan 1 (SAC) indicated intrinsic defects in their resting B cells, while impairment in pokeweed mitogen (PWM)-induced blastogenesis coupled with increased levels of Ig secretion signified regulatory defects in their mature B cells, which may be related to helper-suppressor dysfunctions. Based on these findings, a multifactorial immunodysfunction in AIDS was proposed. The antiviral biological modulator drug isoprinosine was shown to enhance PWM-induced, T-cell dependent, B-cell blastogenesis and normalize the spontaneous secretion of Ig while showing no modulative effects on SAC-induced (resting B-cell) transformations. It also modified, in a selective fashion, the phenotypic coexpression of both HLA-DR and Leu8 antigen on helper and suppressor T cells. Among prodromal subjects at risk to develop AIDS, isoprinosine augmented the expression of both helper T-cell subsets while reducing the number of suppressor effector cells and activated suppressor cells. These interferences with the helper-suppressor regulatory loop may explain the therapeutic efficacy of this drug in the early stages of AIDS.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D006716:Homosexuality; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007288:Inosine / Q000031:analogs & derivatives*; D007542:Inosine Pranobex / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D012016:Reference Values; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000187:drug effects / Q000276:immunology*
D007288:Inosine; D007542:Inosine Pranobex