The IL-12 family of cytokines (IL-12, IL-23, and IL-27) has an important role in inflammation and autoimmune diseases. IL-12 is produced by macrophages and dendritic cells in response to certain bacterial and parasitic infections and is a powerful inducer of IFN-gamma production. IL-23 is proposed to stimulate a subset of T cells to produce IL-17, which in turn induce the production of proinflammatory cytokines that lead to a protective response during infection. IL-27 appears to have duel functions as an initiator of TH1-type (cellular immunity) immune responses and as an attenuator of immune/inflammatory responses.

The present inventions provide methods for improved expression of multimeric proteins by engineering different ratios of the subunit expression units in a cell or upon expression from a multi-promoter plasmid having different strength promoters. The inventors have improved the levels and efficiency of expression of the IL-12 family of cytokines, which includes IL-12, IL-23, and IL-27, by adjusting the transcription and translation of the alpha and beta subunits that comprise the heterodimeric proteins. Optimal ratios of expression for the two (2) subunits were determined for IL-12, IL-23, and IL-27. 0