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 gD in an antigen-specific mode did it exhibit an enhanced protective effect against the sublethal dose of genital HSV-2 challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Bui
T
T
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle 98195.
Faltynek
C R
CR
Ho
R J
RJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy / Q000517:prevention & control; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008081:Liposomes; D011994:Recombinant Proteins / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D015851:Interleukin-7; D008081:Liposomes; D011994:Recombinant Proteins