Interferon Response to Poly IC/Poly-L-Lysine in Normal and Lymphocyte-Suppressed Primates

Abstract

Grivet monkeys immunosuppressed with either cyclophosphamide or methylprednisolone retain their capacity to produce interferon in response to poly I:C/poly-L-lysine (poly ICL). To simulate a human immunosuppressed condition, monkeys were maintained in a lymphocyte suppressed state (500-2200 lymphocytes/mm³, mean = 1550) for five weeks by weekly intravenous injections of cyclophosphamide (50 mg/kg i.V.). Monkeys similarly treated with phosphate buffered saline retained lymphocytes within the normal range (3900-10,000 lymphocytes/mm³, mean = 8320). Both groups produced comparable interferon (IFN) titers in response to weekly induction (iv) with poly ICL. Monkeys injected once with methylprednisolone (15 mg/kg iv) and then induced with poly ICL 4 h later (maximum lymphocyte suppression) retained their full capacity to produce IFN. However, repeated injections of poly ICL in normal grivet monkeys resulted in hyporesponsive IFN production following daily or alternate day injections, but not following injections every third day. Total IFN produced was similar regardless of the frequency of inducer injections. All IFNs produced were similar to human leukocyte interferon (HuIFN-α); e.g., higher antiviral titers on bovine cells than human fibroblasts and neutralization with antisera against IFN-α.