INTERLEUKIN-6 CAN PRIME THP-1 MACROPHAGES FOR ENHANCED PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN RESPONSE TO LPS

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF-alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF-alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1-beta and/or TNF-alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF-alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF-alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1-beta production. In summary, the ability of IL-6 to potentiate TNF-alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.