GM-CSF DNA induces specific patterns of cytokines and chemokines in the skin: implications for DNA vaccines

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing the proliferation, maturation, and migration of dendritic cells, and the expansion and differentiation of B and T lymphocytes. Similar biological effects have been observed with the use of GM-CSF DNA in mouse models for therapy of cancer and infectious diseases, and its use is currently being investigated in clinical trials in combination with DNA vaccines. To further understand the adjuvant mechanisms of GM-CSF DNA, we examined early events following its administration. We found measurable levels of GM-CSF protein in the skin and muscle, as well as in serum. Measurements of other cytokine and chemokine levels revealed differential expression patterns over time. The early response was characterized by high levels of inflammatory molecules, including IL-1β, IL-6, TNFα, RANTES, MIP-1α and MCP-1, later followed by expression of precursor Th1 cytokines, IL-12 and IL-18, concomitant with IFNγ production. Local produ...