Secretion of interleukin-6 (IL-6)by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha

• Published in: Immunology 1990, Vol.69 (1), p.52-56
• Main Authors: SANCEAU, J, FALCOFF, R, BERANGER, F, CARTER, D. B, WIETZERBIN, J
• Format: Article
• Language: English
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Blotting, Northern; Cells, Cultured; Drug Synergism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression - immunology; Humans; Immunobiology; Interleukin-6 - analysis; Interleukin-6 - genetics; Lymphokines, interleukins ( function, expression); Monocytes - drug effects; Monocytes - immunology; Regulatory factors and their cellular receptors; RNA - analysis; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0019-2805; 1365-2567

We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.