BIOLOGICAL RESPONSE OF RECOMBINANT INTERLEUKIN-7 ON HERPES-SIMPLEX VIRUS-INFECTION IN GUINEA-PIGS

We investigated the biological activity of human recombinant interleukin-7 (rhIL-7) on guinea-pig cells in vitro and in vivo. RhIL-7 can stimulate plastic non-adherent cells of guinea-pigs to proliferate in vitro at a degree comparable to that of human cells. Administration of rhIL-7 to guinea-pigs significantly increased their white blood cell concentration, specifically the lymphocyte population. The effect of rhIL-7 on circulating blood cells was dose dependent, in that 14 doses of twice daily subcutaneous injections at 8 x 10(5) U kg(-1) and 2.4 x 10(6) U kg(-1) rhIL-7 increased peripheral blood lymphocyte concentrations by 38% (p = 0.047) and 139% (p = 0.0005), respectively, compared with the placebo group. Two weekly doses of rhIL-7 liposome (5.6 x 10(6) U kg(-1) dose, equivalent to 11.2 x 10(6) U kg(-1) total dose) elicited a similar effect on the lymphocyte population, comparable to that of the twice daily administrations of 8 x 10(5) U kg(-1) soluble rhIL-7 for 7 days (7 days x two doses/day x 8 x 10(5) U kg(-1) = 11.2 x 10(6) U kg(-1) total dose). However, the increased lymphocyte count induced by rhIL-7 administration did not protect guinea-pigs from the primary herpes simplex virus (HSV)-2 infection. Only when rhIL-7 was given in association with HSV-antigen go in an antigen-specific mode did it exhibit an enhanced protective effect against the sublethal dose of genital HSV-2 challenge. Our results show that immunogenicity of alum-associated HSV-gD can be enhanced by co-administration of rhIL-7 liposome formulation to reduce significantly the severity and course of the primary HSV-2 infection.