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

We investigated the biological activity of human recombinant interleuk in-7 (rhIL-7) on guinea-pig cells in vitro and in vivo. RhIL-7 can sti mulate plastic non-adherent cells of guinea-pigs to proliferate in vit ro at a degree comparable to that of human cells. Administration of rh IL-7 to guinea-pigs significantly increased their white blood cell con centration, 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 concentratio ns by 38% (p = 0.047) and 139% (p = 0.0005), respectively, compared wi th 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) elicit ed a similar effect on the lymphocyte population, comparable to that o f 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 induce d by rhIL-7 administration did not protect guinea-pigs from the primar y herpes simplex virus (HSV)-2 infection. Only when rhIL-7 was given i n association with HSV-antigen go in an antigen-specific mode did it e xhibit an enhanced protective effect against the sublethal dose of gen ital HSV-2 challenge. Our results show that immunogenicity of alum-ass ociated HSV-gD can be enhanced by co-administration of rhIL-7 liposome formulation to reduce significantly the severity and course of the pr imary HSV-2 infection.