In this study we examined the in vitro effects of alcohol on the proli
ferative responses of lymphocytes from healthy donors and AIDS patient
s to a recombinant fusion peptide, env-gag, corresponding to portions
of the gp 41 envelope (env) and internal core (gag) proteins of HIV. T
he effects of alcohol (ETOH) on the natural killer (NK) cell activitie
s of lymphocytes from healthy donors and patients with AIDS were also
investigated. Peripheral blood mononuclear cells from both normal dono
rs and AIDS patients produced significant levels of lymphocyte prolife
rative responses to the HIV env-gag peptide; however, these responses
were significantly higher in patients with AIDS, showing the specifici
ty of the response. The env-gag-induced proliferative responses of lym
phocytes from normal subjects were significantly suppressed when cultu
res contained only higher levels of ETOH (0.2% and 0.3%), whereas ETOH
even at a lower level (0.1%) produced significant suppression of the
env-gag-induced proliferation of lymphocytes only from AIDS patients.
Direct addition of ETOH at concentrations of 0.1%, 0.2%, and 0.3% to c
ultures of lymphocytes from normal donors and NK target cells did not
produce significant suppression of NK cell activities. However, ETOH a
t concentrations of 0.2% and 0.3% significantly suppressed the NK acti
vities of lymphocytes from AIDS patients, and the suppressive effect w
as observed at all E:T cell ratios examined. Control peptide from the
Escherichia coli expression vector did not produce any significant eff
ect on lymphocyte proliferative responses or NK activity of both norma
l donors and AIDS patients. ETOH at various concentrations (0.1%, 0.2%
, and 0.3%) or env-gag (10 ng/ml), when individually added to cultures
of NK effector and target cells and allowed to remain throughout the
4-h assay period, produced no significant suppression of the NK activi
ty of normal lymphocytes. This suggests a selective inhibitory effect
of ETOH on lymphocyte proliferative responses and NK activity of lymph
ocytes from AIDS patients. Thus ETOH at intoxicating levels may have i
mmunomodulatory effects on the host's immune responses to HIV infectio
n.