The effects of highly purified and/or recombinant interferon (IFN)-α/β, IFN-α, IFN-β, IFN-γ, and the IFN-inducer, poly(I):poly(C), on the circulation of peripheral blood leukocytes (PBL) and thoracic duct lymphocytes (TDL) of (BALB/cJ × C57B1/6J)F1 mice were examined. Although all IFN classes could depress significantly the number of circulating PBL and TDL when given at sufficient doses, IFN-α appeared to be the most potent. Phenotypic analysis of lymphocytes in the blood and lymph during the decrease induced by IFN suggests that IFN-α/β and IFN-α preferentially decrease the Lyt-2+, or suppressor/cytotoxic, subset. Timing of IFN administration was found to be an important factor. Repeated administration of IFN-α/β once a day for 3 days produced continuous suppression of the number of circulating PBL. Administration of either IFN-α/β or IFN-γ in the evening resulted in a longer and more extensive inhibition of PBL circulation than when IFN was administered in the morning. Our results suggest that the leukopenia observed in many patients undergoing IFN therapy may, in part, be attributed to decreased lymphocyte recirculation, and that the timing of IFN administration may be important in maximizing its therapeutic index.
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