Cytokine responses of human blood monocytes stimulated with Igs

Using an in vitro system for stimulating human peripheral blood mononuclear cells (PBMC) with immobilized Ig, patterns of cytokine production as a function of different Ig classes and subclasses were elucidated. Wells were coated with IgA, IgG1, IgG2, IgG3 or IgG4. Equivalent protein content on surfaces of wells was demonstrated by a human kappa chain ELISA. Isolated human PBMC were added to Ig-coated wells and incubated for 24 hrs before supernatants were assayed for cytokines. The IgG subclasses showed differences in cytokine production stimulated from PBMC, with the relative stimulation for TNF alpha being IgG2 greater than or equal to IgG3 greater than or equal to IgG1 > IgG4 and for IL-6 production, IgG2 greater than or equal to IgG3 > IgG1 = IgG4. In contrast, the relative stimulation for IL-8 was IgG1 = IgG2 = IgG3 = IgG4. IgA caused less production of TNF alpha when compared to IgG2, but similar levels of IL-8. Such differences may have important implications in the pathogenesis of immune complex mediated diseases.