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 plas mid DNA is taken up by myofibers and subsequently expresses exogenous genes, In the present study, we assessed intramuscular DNA injection a s a means of systemically delivering interleukin-5 (IL-5), We construc ted an IL-5 expression plasmid, pCAGGS-IL-5, containing murine IL-5 cD NA under the control of the CAG promoter, The soleus muscle of mice wa s 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 we eks 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-I L-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 inje cted with pCAGGS-IL-5, but in none of the control mice, These results demonstrate that intramuscular plasmid injection serves as a useful me thod of systemically delivering cytokines by combining the strong CAG promoter and bupivacaine pretreatment. (C) 1997 Academic Press.