Conditioned immune response to interferon-gamma in humans

We determined whether a classical conditioning paradigm may be used to cond ition immunologic responses in normal human subjects receiving an optimal i mmunostimulating dose of recombinant human interferon-gamma (rhIFN-gamma). We conducted a placebo-controlled, double-blind study of 31 normal voluntee rs in order to determine whether an initially immune-neutral stimulus, oral propylene glycol (PG), could eventually elicit an immune response as a con sequence of its being paired with a known immunostimulatory dose and schedu le of rhIFN-gamma. Subjects were randomly assigned to one of three groups: (A) rhIFN-gamma injections paired with PG; (B) normal saline injections pai red with PG; (C) rhIFN-gamma injections alone. During the 4-week study, sub jects received progressively fewer injections so that, by the final week of the study, no injections were given and groups A and B received only PG. T he principal outcome measures were serum concentrations of quinolinic acid (QUIN) and neopterin, two nonspecific but sensitive markers of immune activ ation, and expression of Fc receptors (CD64) on peripheral blood mononuclea r cells. RhIFN-gamma injections produced significant and predictable altera tions in each of the measured immune parameters. No group B subject made an immune response. Mean serum QUIN levels were significantly higher at the e nd of week three for subjects in the experimental condition (group A) than for subjects receiving rhIFN-gamma alone (group %) despite receiving identi cal doses of rhIFN-gamma. Similarly, the predicted decay in mean serum neop terin levels from the end of week 1 to the end of week 2 was seen in group C but not in group A. The exposure of group A to PG blunted the decline of CD64 expression in week four. The data suggest that the pairing of an uncon ditioned stimulus (rhIFN-gamma) and a conditioned stimulus (PG) permits the conditioned stimulus alone to prolong a cytokine-induced response in norma l humans.