Intramuscular injection of expression plasmid DNA is an effective means of long-term systemic delivery of interleukin-5.
It has been demonstrated that intramuscularly injected expression plasmid DNA is taken up by myofibers and subsequently expresses exogenous genes. In the present study, we assessed intramuscular DNA injection as a means of systemically delivering interleukin-5 (IL-5). We constructed an IL-5 expression plasmid, pCAGGS-IL-5, containing murine IL-5 cDNA under the control of the CAG promoter. The soleus muscle of mice was pretreated with bupivacaine. Two days later, mice were injected with pCAGGS-IL-5 or a control pCAGGS plasmid DNA at the same site. At 2 weeks after DNA injection, eosinophils had increased from 2-3% to 8-29% of peripheral white blood cells in 9 of 10 mice injected with pCAGGS-IL-5, while eosinophils never exceeded 3% in control mice injected with pCAGGS. IL-5 mRNA was present in the muscle area injected with pCAGGS-IL-5. IL-5 was also detectable by ELISA in the sera of most mice injected with pCAGGS-IL-5, but in none of the control mice. These results demonstrate that intramuscular plasmid injection serves as a useful method of systemically delivering cytokines by combining the strong CAG promoter and bupivacaine pretreatment.
Tokui
M
M
Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Takei
I
I
Tashiro
F
F
Shimada
A
A
Kasuga
A
A
Ishii
M
M
Ishii
T
T
Takatsu
K
K
Saruta
T
T
Miyazaki
J
J
D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D007273:Injections, Intramuscular; D015848:Interleukin-5 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D015848:Interleukin-5; D012333:RNA, Messenger