CYTOKINE RESPONSES OF HUMAN BLOOD MONOCYTES STIMULATED WITH IGS

Using an in vitro system for stimulating human peripheral blood mononu clear cells (PBMC) with immobilized Ig, patterns of cytokine productio n as a function of different Ig classes and subclasses were elucidated . Wells were coated with IgA, IgG1, IgG2, IgG3 or IgG4. Equivalent pro tein content on surfaces of wells was demonstrated by a human kappa ch ain ELISA. Isolated human PBMC were added to Ig-coated wells and incub ated for 24 hrs before supernatants were assayed for cytokines. The Ig G 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 con trast, the relative stimulation for IL-8 was IgG1 = IgG2 = IgG3 = IgG4 . IgA caused less production of TNF alpha when compared to IgG2, but s imilar levels of IL-8. Such differences may have important implication s in the pathogenesis of immune complex mediated diseases.