Correlation of the suppressive activity of a biological response modifier on the proliferation of peripheral blood mononuclear cells and the reduction of HIV titer.
Activation of CD4+ cells is a prerequisite for infection by the human immunodeficiency virus (HIV). Thus, any agent capable of suppressing CD4+ cell proliferation could create a refractory stage that would impede viral infection. We have reported, in a previous publication, that a biological response modifier (BRM), polyantigenic immunomodulator (PAI) substantially reduces HIV-1 titer (from 20 to 100%) in peripheral mononuclear cells (PBMC) cultures with high viral titer (p24 = 10(2)-10(5) pg/ml). We are presenting data suggesting that the reported reduction in virus titer seems to be associated with a suppressive activity of PAI on the proliferation of PBMC from intravenous drug users (IVDU) infected and non-infected with HIV-1. PAI, a well characterized BRM, is a mixture of inactivated bacterial and influenza virus vaccines. PBMC from healthy donors and IVDU individuals were exposed to PAI, phytohemagglutinin (PHA), interleukin-2 (IL-2) and to combinations of PAI with either PHA or IL-2. Appropriate controls were included. 3H-thymidine pulsing was used as indicator of cell proliferation. The stimulation index and the difference between mean cpm of test sample and control were used to measure proliferative activity. There was a low proliferative response in the PBMC cultures from IVDU and HIV-1 positive patients, but it was substantially lower in the later group. When PBMC cultures from the same group of individuals were exposed to PAI, PHA and IL-2, and to the combination of either PAI plus PHA or IL-2, the response observed in the PAI treated group was uniformly lower than in the other treated cultures. Moreover, when PAI was combined with PHA, it exerted a significant reduction in the measured parameters. The effect of PAI on IL-2 activity was negligible. A suppressive effect of a PAI has been detected on the proliferation of PBMC from IVDA and HIV-1 positive individuals. This activity may be associated with the capacity of PAI to reduce HIV titers in infected PBMC cultures.