Modulation of virus-induced delayed-type hypersensitivity by plasmid DNA encoding the cytokine interleukin-10.
This report evaluates the efficacy of eukaryotic expression plasmids encoding cytokines at modulating the induction and expression of cutaneous delayed-type hypersensitivity (DTH) responses to virus infections. Mice given a single intramuscular administration of cytokine DNA were subsequently infected with either herpes simplex virus (HSV) or vaccinia virus, then tested for DTH. Responses in animals given interleukin-10 DNA were markedly suppressed for at least 5 weeks after pretreatment. Animals also expressed diminished T-cell proliferative responses and modest changes in the balance of T helper type 1 and 2 T-cell reactions. Treatment of animals already sensitized to express DTH, also showed inhibited responses, these taking 6-7 days after treatment to become apparent. Our results show the potency and convenience of plasmid DNA encoding cytokines to modulate inflammatory reactions. Advantages and risks of the cytokine DNA approach are briefly discussed.
Manickan
E
E
Department of Microbiology, University of Tennessee, Knoxville 37996-0845, USA.
Daheshia
M
M
Kuklin
N
N
Chun
S
S
Rouse
B T
BT
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000627:therapeutic use*; D014615:Vaccinia / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10