Enkephalins have been shown to enhance T cell-mediated immune responses and natural killer-cell activity in vitro. We have studied the effects of infusions of
methionine-enkephalin on immune functions and clinical courses in seven patients with various stages of
infection with human immunodeficiency virus (HIV). All patients were clinically stable at the time of entry into the study. Each received 10 micrograms/kg of
methionine-enkephalin in an
intravenous infusion three times weekly for up to 12 weeks. Evaluation of cellular immunity (T-cell subsets, in vitro
interleukin-2 production and
interleukin-2 receptor expression, T-cell responses to
mitogens and
antigens, and
delayed-hypersensitivity skin tests) as well as clinical and toxicity monitoring was performed prior to treatment, at 2-week intervals during treatment, and after the
cessation of treatment. Increases in
interleukin-2 receptor expression were seen on lymphocytes collected on one occasion from each of two patients 30 min postinfusion. Studies done 24 hr after infusions revealed increases in
interleukin-2 production in one patient, but when pre- and posttreatment values were compared there were no significant changes in numbers of circulating T cells of any phenotype or in T-cell responses to
mitogens or
antigens. None of the patients with
Kaposi's sarcoma had regression of
tumor; one patient dropped out of the study at week 5 because of deteriorating clinical status and progression of
tumor. There were no adverse reactions or evidence of toxicity. We conclude that
methionine-enkephalin appears to enhance temporarily selected immune responses in patients with
HIV infection, however, in the schedule used in this study it was not clinically efficacious.