Six healthy volunteers were given single intramuscular injections of an ascending dose schedule of human interferon alpha 2 (Hu IFN alpha 2) from Escherichia coli. At a dose of 3 X 10(6) U, all of the volunteers had febrile reactions with influenza-like symptoms as previously described for purified natural leukocyte interferon. Significant rises in serum 11-hydroxycorticosteroids and falls in plasma zinc levels were observed at this highest dose. Although there was a reduction in the febrile reaction complex, the simultaneous administration of indomethacin with a "toxic" dose of interferon did not alter the changes in white cells, corticosteroids, or trace metals. Nonspecific effects must be considered in the therapeutic activity of interferon
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