Abstract
Leukotriene B4 (LTB4) preferentially induced IL-6 mRNA accumulation and IL-6 protein release as assessed by ELISA and the B9 cell bioassay. In contrast, minimal IL-1 mRNA or protein was induced by LTB4 either in the absence or presence of muramyl dipeptide. Supernatants of LTB4-treated monocytes consistently showed enhanced thymocyte costimulatory activity and this was abrogated by 75–80% by anti-IL-1 antibody. Baseline production of IL-1 appeared however to be sufficient for a synergistic stimulation of thymocytes in the presence of IL-6. Our results now help clarify that LTB4 stimulated preferentially IL-6 production and that the observed LTB4-induced augmentation in thymocyte responses to monocyte supernatants is due to augmented IL-6 contents in the presence of baseline minimal IL-1 production.
Similar content being viewed by others
References
M. Rola-Pleszczynski,Immunoregulation by leukotrienes and other lipoxygenase metabolites. Immunol. Today.10, 302–307 (1985).
C. Dubois, E. Bissonnette and M. Rola-Pelszczynski,Platelet-activating factor (PAF) stimulates tumor necrosis factor production by alveolar macrophages: prevention by PAF receptor antagonists and lipoxygenase inhibitors. J. Immunol.143, 964–969 (1989).
M. Rola-Pleszczynski and I. Lemaire,Leukotrienes augment interleukin-1 production by human monocytes. J. Immunol.135, 3958–3961 (1985).
M. Lotz, F. Junk, P. Kabourides, C. Tsoukas, T. Hirano, T. Kishimoto and D. Carson,B cell stimulatory factor 2/interleukin-6 is a costimulant for human thymocytes and T lymphocytes. J. Exp. Med.167, 1253–1264 (1988).
L. Aarden, E. R. DeGroot, O. L. Schapp and P. M. Lansdorp,Production of hybridoma growth factor by human monocytes. Eur. J. Immunol.17, 1411–1415 (1987).
A. Böyum,Isolation of mononuclear cells and granulocytes from human blood. Scand. J. Lab. Invest. (suppl)21, 77–89 (1968).
P. E. Poubelle, P. Borgeat and M. Rola-Pleszczynski,Assessment of leukotriene B 4 synthesis in human lymphocytes by using high performance liquid chromatography and radioimmunoassay methods. J. Immunol.139, 1273–1277 (1987).
S. B. Mizel, J. J. Oppenheim and D. L. Rosenstreich,Characterization of lymphocyte-activating factor (LAF) produced by the macrophage cell line P388D. Enhancement of LAF production by activated T lymphocytes. J. Immunol.120, 1497–1503 (1978).
J. Grassi, Y. Frobert, P. Pradelles, F. Chercuitte, D. Gruaz, J.-M. Dayer and P. E. Poubelle,Production of monoclonal antibodies against interleukin-1α and-1β. Development of two enzyme immunometric assays (EIA) using acetylcholinesterase and their application to biological media. J. Immunol. Meth.123, 193–210 (1989).
P. Chomczynski and N. Sacchi,Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem.162, 156–165 (1987).
L. Singh and K. W. Jones,The use of heparin as a simple cost effective means of controlling background in nucleic acid hybridization procedures. Nucleic Acids Res.12,5627–5634 (1984).
H. Mitzutani, L. T. May, P. B. Seghal and T. S. Kupper,Synergistic interactions of IL-1 and IL-6 in T cell activation. Mitogen but not antigen receptor-induced proliferation of a cloned T helper cell line is enhanced by exogenous IL-6. J. Immunol.143, 896–902 (1989).
R. Schindler, J. Mancilla, S. Endres, R. Ghorbani, S. C. Clark and C. A. Dinarello,Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood.75, 40–49 (1990).
J. Content, L. De Wit, P. Poupart, G. Opdenakker, J. Van Damme and A. Billiau,Induction of 26-kDa-protein mRNA in human cells treated with an interleukin-1 related, leukocyte — derivated factor. Eur. J. Biochem.152, 253–257 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poubelle, P.E., Stankova, J., Grassi, J. et al. Leukotriene B4 up-regulates IL-6 rather than IL-1 synthesis in human monocytes. Agents and Actions 34, 42–45 (1991). https://doi.org/10.1007/BF01993233
Issue Date:
DOI: https://doi.org/10.1007/BF01993233