Acute Genital Infection in Guinea Pigs: Effect of Recombinant Interleukin-2 on Herpes Simplex Virus Type 2

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Abstract
Human recombinant interleukin-2 (rIL-2) modifies infection with herpes simplex virus type 2 (HSV-2) in normal guinea pigs. Animals were injected sc with rIL-2 twice a day, beginning 24 hr before infection and continuing for three subsequent days. Guinea pigs were assigned to five different regimens in which rIL-2 was administered daily at dosages from 8 × 103 U/kg to 8 × 105 U/kg. After intravaginal inoculation with HSV-2, 83% of 24 control animals developed apparent genital herpes, and 5% had asymptomatic viral shedding. Animals receiving 4 × 104 U or 2 × 105 U of rIL-2/kg showed a significantly lower rate of infection (P < .001 by χ2 ) and a lower number of lesions and more rapid healing than did the infected animals in the control (untreated) group. The mortality in the untreated group(28%) was higher than in the animals in the 2 × 105 U/kg treatment group (7%). No difference was observed between the control, the 8 × 103 U/kg, and the 8 × 1O5 U/kg treatment groups with respect to severityof infection or mortality. Animals examined two to four weeks after inoculation had lymphocyte stimulation indices (induced with HSV-2 antigen) >3.5 and titers of antibody between 2.5 log1O and 4.5 log1O by radioimmunoassay. In the disease-free animals, stimulation indexes were P < .05) in the 2 × 105 U/kg treatment group. Thus, IL-2 protected against acute HSV-2 infection in guinea pigs with a biphasic dose response that peaked between 4 × 104 U/kg and 2 × 105 U/kg. Animals escaping infection after treatment with rIL-2 appeared to lack immunologic memory to HSV-2, and those developing disease showed only mild-to-moderate lesions that paralleled the diminished lymphocyte responses to HSV-specific antigens.