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Production of tumor necrosis factor, interleukin-6 and prostaglandin E2 by LPS-stimulated rat bone marrow macrophages after thermal injury: Effect of indomethacin

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Abstract

The effect of thermal injury on the in vitro production of TNF, IL-6, and PGE2 by bone marrow-derived, LPS-stimulated rat macrophages was studied. Thermal injury caused a general hyperactivity in the production of the mediators by the cells. Indomethacin, a cyclooxygenase inhibitor of PGE2 synthesis, inhibited the production of IL-6 and PGE2 but had no effect on the production of TNF. These results suggest that the observed low concentration of PGE2 produced by the cells was insufficient to cause inhibition of TNF synthesis; thus, the effect of indomethacin would be undetectable. The results also suggest that indomethacin may act directly in inhibiting the production of IL-6 by the macrophages. The hyperactive effect of thermal injury on the production of inflammatory mediators by newly differentiated bone marrow derived macrophages can be important in the overall systemic response to the insult.

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References

  1. Goud, T. J., C. Schotte, andR. VanFurth. 1975. Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro.J. Exp. Med. 142:1180–1199.

    PubMed  Google Scholar 

  2. VanFurth, R., J. A. Raeburn, andT. L. VanZwet. 1979. Characteristics of human mononuclear phagocytes.Blood 54:485–500.

    PubMed  Google Scholar 

  3. Volkman, A., andF. M. Collins. 1974. The cytokinetics of monocytes in acuteSalmonella infection in the rat.J. Exp. Med. 139:264–277.

    PubMed  Google Scholar 

  4. Hume, D. A., W. Allan, B. Fabrus, M. J. Weidemann, A. J. Hapel, andS. Bartelmez. 1987. Regulation of proliferation of bone marrow-derived macrophages.Lymphokine Res. 6:127–139.

    PubMed  Google Scholar 

  5. Le, P. T., J. Kartzburg, S. J. Brandt, J. E. Niedel, B. F. Haynes, andK. H. Singer. 1988. Human thymic epithelial cells produce granulocyte and macrophage colony-stimulating factors.J. Immunol. 141:1211–1216.

    PubMed  Google Scholar 

  6. Cline, M. J., andM. A. Sumner. 1972. Bone marrow macrophage precursors. I. Some functional characteristics of the early cells of the mouse macrophage series.Blood 40:62–69.

    PubMed  Google Scholar 

  7. O'Reilly, M., andR. L. Gamelli. 1990. Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment.Exp. Hematol. 18:974–978.

    PubMed  Google Scholar 

  8. Dexter, T. M., andE. Spooncer. 1987. Growth and differentiation in the hemopoietic system.Annu. Rev. Cell Biol. 3:423–439.

    PubMed  Google Scholar 

  9. Sodhi, A., R. K. Singh, andK. Pai. 1990. Activation of murine macrophages by tumor necrosis factor, interleukin-1, interferon-γ and cisplatin.Immunol. Lett. 26:45–50.

    PubMed  Google Scholar 

  10. Falk, L. A., L. M. Wahl, andS. N. Vogel. 1988. Analysis of la antigen expression in macrophages derived from bone marrow cells cultured in granulocyte-macrophage colonystimulating factor or macrophage colony-stimulating factor.J. Immunol. 140:2652–2660.

    PubMed  Google Scholar 

  11. Heidenreich, S., J.-H. Gong, A. Schmidt, M. Nain, andD. Gemsa. 1989. Macrophage activation by granulocyte/macrophage colony-stimulating factor.J. Immunol. 143:1198–1205.

    PubMed  Google Scholar 

  12. VanSnick, J. 1990. Interleukin-6: An overview.Annu. Rev. Immunol. 8:253–278.

    PubMed  Google Scholar 

  13. Beutler, B., andA. Cerami. 1986. Cachectin and tumor necrosis factor as two sides of the biological coin.Nature 320:584–588.

    PubMed  Google Scholar 

  14. Marano, M. A., L. I. Moldawer, Y. Fong, H. Wei, J. Minei, R. Yurt, A. Cerami, andS. F. Lowry. 1988. Cachectin/TNF production in experimental burns and Pseudomonas infection.Arch. Surg. 123:1383–1388.

    PubMed  Google Scholar 

  15. Piguet, P. F., G. E. Grau, andP. Vassalli. 1991. Tumor necrosis factor and immunopathology.Immunol. Res. 10:122–140.

    PubMed  Google Scholar 

  16. Ertel, W., M. H. Morrison, A. Ayala, andI. H. Chaudry. 1991. Eicosanoids regulate tumor necrosis factor synthesis after hemorrhage in vitro and in vivo.J. Trauma 31(5):609–616.

    PubMed  Google Scholar 

  17. Rasmussen, L. T., P. E. Lipsky, andR. Seljelid. 1987. Production of PGE2 and IL-1 by mouse peritoneal macrophages stimulated with beta 1,3-d-glucan derivatized plastic beads.Scand. J. Immunol. 26:731–736.

    PubMed  Google Scholar 

  18. Goodwin, J. S., andD. R. Webb. 1980. Regulation of the immune response by prostaglandins.Clin. Immunol. Immunopathol. 15:106–122.

    PubMed  Google Scholar 

  19. Knapp, W., andG. Baumgartner. 1978. Monocyte-mediated suppression of human B lymphocyte differentiation in vitro.J. Immunol. 121:1171–1183.

    Google Scholar 

  20. Homo-Delarche, F., D. Duval, andM. Papiernik. 1985. Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids.J. Immunol. 135(1):506–511.

    PubMed  Google Scholar 

  21. Bray, M. A., andD. Gordon. 1978. Prostaglandin production by macrophages and the effect of anti-inflammatory drugs.Br. J. Pharmacol. 63:635–642.

    PubMed  Google Scholar 

  22. O'Riordain, M. G., H. H. Collins, M. Pitz, I. B. Saporoschetz, J. A. Mannick, andM. L. Rodrick. 1992. Modulation of macrophage hyperactivity improves survival in a burn-sepsis model.Arch. Surg. 127:152–157.

    PubMed  Google Scholar 

  23. Faist, E., W. Ertel, T. Cohnert, P. Huber, D. Inthorn, andG. Heberer. 1990. Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma.J. Trauma 30:8–17.

    PubMed  Google Scholar 

  24. Faist, E., A. Markewitz, D. Fuchs, S. Lang, S. Zarius, F.-W. Schildberg, H. Wachter, andB. Reichart. 1991. Immunomodulatory therapy with thymopentin and indomethacin.Ann. Surg. 214:264–275.

    PubMed  Google Scholar 

  25. Akira, S., T. Hirano, T. Taga, andT. Kishimoto. 1990. Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF).FASEB J. 4:2860–2867.

    PubMed  Google Scholar 

  26. Fong, Y., L. L. Moldawer, M. Marano, H. Wei, S. B. Tatter, R. H. Clarick, U. Santhanam, D. Sherris, L. T. May, P. B. Sehgal, andS. F. Lowry. 1989. Endotoxemis elicits increased circulating β2-IFN/IL-6 in man.J. Immunol. 142:2321–2324.

    PubMed  Google Scholar 

  27. McNiece, I. K., F. M. Stewart, D. M. Deacon, andP. J. Quesenberry. 1988. Synergistic interactions between hematopoietic growth factors as detected by in vitro mouse bone marrow colony formation.Exp. Hematol. 16:383–388.

    PubMed  Google Scholar 

  28. Metcalf, D., S. Merchav, andG. Wagemaker. 1982. Commitment by GM-CSF or M-CSF of biopotential GM progenitor cells to granulocyte or macrophage formation.In Experiments in Hematology Today. S. J. Baum, G. D. Ledney, and S. Thierfeldman, editors. S. Karger, Basel. 3–9.

    Google Scholar 

  29. Bartelmez, S. H., andE. R. Stanley. 1985. Synergism between hemopoietic growth factors (HGFs) detected by their effect on cells bearing receptors for a lineage specific HGF: Assay of hemopoietin-1.J. Cell. Physiol. 122:370–378.

    PubMed  Google Scholar 

  30. Ikebuchi, K., G. G. Wong, S. C. Clark, J. N. Ihle, Y. Hirai, andM. Ogawa. 1987. Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotent hemopoietic progenitors.Proc. Natl. Acad. Sci. U.S.A. 84:9035–9039.

    PubMed  Google Scholar 

  31. Stanley, E. R., A. Bartocci, D. Patinkin, M. Rosendaal, andT. R. Bradley. 1986. Regulation of very primitive, multipotent hemopoietic cells by hemopoietin-1.Cell 45:667–674.

    PubMed  Google Scholar 

  32. Shacter, E., G. K. Arzadron, andJ. Williams. 1992. Elevation of Interleukin-6 in response to a chronic inflammatory stimulus in mice: Inhibition in indomethacin.Blood 80(1): 194–202.

    PubMed  Google Scholar 

  33. Ogle, C. K., X. Guo, andJ. D. Ogle. 1993. The production of cytokines and PGE2 and the cytotoxicity of stimulated bone marrow macrophages after thermal injury and the cytotoxicity of stimulated U-937 macrophages.Inflammation 17:583–594.

    PubMed  Google Scholar 

  34. Ogle, C. K., X. Guo, J. W. Alexander, R. Fukushima, andJ. D. Ogle. 1993. The activation of bone marrow macrophages 24 hours after thermal injury.Arch. Surg. 128:96–101.

    PubMed  Google Scholar 

  35. Aarden, L. A., E. R. DeGroot, O. L. Schaap, R. Spengler, J. Larrick, D. Remick andP.M. Lansdorp. 1987. Production of hybridoma growth factor by human monocytes.Eur. J. Immunol. 17:1411–1416.

    PubMed  Google Scholar 

  36. Ruff, M. R., andG. E. Gifford. 1993. Tumor necrosis factor.In Lymphokines. E. Pick, editor. Academic Press, New York. 235–273.

    Google Scholar 

  37. Koerner, T. J., andD. O. Adams. 1989. Gene regulation in macrophage development and activation.Yearbook Immunol. 4:159–180.

    Google Scholar 

  38. Yu, S-F., T. J. Koerner, andD. O. Adams. 1990. Gene regulation in macrophage activation: Differential regulation of genes encoding for tumor necrosis factor, interleukin-1, JE, and KC by interferon-gamma and lipopolysaccharide.J. Leukocyte Biol. 48:412–419.

    PubMed  Google Scholar 

  39. Imamura, K., D. Spriggs, andD. Kufe. 1987. Expression of tumor necrosis factor receptors on human monocytes and internalization of receptor bound ligand.J. Immunol. 139:2989–2992.

    PubMed  Google Scholar 

  40. Kunkel, S. L., S. W. Chensue, andS. H. Phan. 1986. Prostaglandins as endogenous mediators of interleukin-1 production.J. Immunol. 136:186–192.

    PubMed  Google Scholar 

  41. Dinarello, C. A., S. O. Marnoy, andL. J. Rosenwasser. 1983. Role of arachidonate metabolism in the immunoregulatory function of human leukocyte pyrogen/lymphocyte activating factor/interleukin 1.J. Immunol. 130:890–895.

    PubMed  Google Scholar 

  42. Kunkel, S. L., M. Spengler, M. A. May, 1988. Prostaglandin E2 regulates macrophagederived tumor necrosis factor gene expression.J. Biol. Chem. 263:5380–5384.

    PubMed  Google Scholar 

  43. Ertel, W., M. H. Morrison, P. Wang, F. Zheng, A. Ayala, andI. H. Chaudry. 1991. The complex pattern of cytokines in sepsis.Ann. Surg. 214(2): 141–148.

    PubMed  Google Scholar 

  44. Ogle, C. K., J.-Z. Wu, S. Wood, J. D. Ogle, J. W. Alexander, andG. D. Warden. 1990. The increased release of prostaglandin E2 by Kupffer cells from burned guinea pigs.J. Burn Care Rehabil. 11(4):287–294.

    PubMed  Google Scholar 

  45. Watanabe, S., K. Onozaki, S. Yamamoto, andH. Okuyama. 1993. Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages.J. Leukocyte Biol. 53:151–156.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, Ohio

    Cora K. Ogle

  2. Cincinnati Unit, Shriners Burns Institute, 45229, Cincinnati, Ohio

    Cora K. Ogle, Xialing Guo, Kathy Szczur, Sharon Hartmann & James D. Ogle

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Ogle, C.K., Guo, X., Szczur, K. et al. Production of tumor necrosis factor, interleukin-6 and prostaglandin E2 by LPS-stimulated rat bone marrow macrophages after thermal injury: Effect of indomethacin. Inflammation 18, 175–185 (1994). https://doi.org/10.1007/BF01534558

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