title: Acyclovir treatment of skin lesions results in immune deviation in mice infected cutaneously with herpes simplex virus.
abstract: Clinical observations indicate that the antibody response to herpes simplex virus (HSV) in patients undergoing acyclovir treatment is reduced and, although the exact mechanism is not clear, some authors interpret it as immunosuppression. In order to clarify the mechanism, we cutaneously infected mice with HSV-1 and treated the resulting skin lesions with acyclovir. The immune response to infection and treatment in these mice was then analysed. Acyclovir treatment was given orally (20 mg/kg, three times daily), starting on day 0 (D0), 2 (D2) or 4 (D4) after infection and continuing until day 10. The serum antibody titre and the severity of skin lesions were significantly higher in the shortest treatment group (D4) than in the longer treatment groups (D0 and D2). In contrast, a skin test analysing delayed-type hypersensitivity (DTH) to HSV antigen showed that the D0 and D2 groups exhibited stronger DTH than the D4 group. Acyclovir treatment failed to cause a dissociation between DTH and antibody production in mice immunized with inactivated HSV antigen. However, acyclovir treatment in infected mice suppressed the development of skin lesions and resulted in a dissociation between DTH response and antibody production, indicating a typical immune deviation. This was supported by a change in the ratio of the isotype antibody IgG2a to IgG1. The treatment of skin lesions with acyclovir reduced the level of antibody response, as observed clinically. This indicates that the reduced antibody response in patients treated with acyclovir may be, at least in part, due to immune deviation and not immunosuppression.
authors.affiliation: Department of Virology, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: S
authors.initials: S
authors.lastname: Kageyama
authors.forename: T
authors.initials: T
authors.lastname: Kawana
authors.forename: K
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000212:Acyclovir / Q000009:adverse effects* / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000009:adverse effects* / Q000494:pharmacology*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018259:Herpesvirus 1, Human; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D000212:Acyclovir