Agents and Actions

, Volume 36, Issue 1–2, pp 66–69 | Cite as

The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells

  • A. Erroi
  • M. Bianchi
  • P. Ghezzi
Inflammation and Immunomodulation


Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of bleomycin- and silica-induced lung damage. We have studied the effect of paraquat (PQ), a well-known pneumotoxicant, on IL-1 and TNF production by human peripheral blood mononuclear cells from different healthy donors stimulated with endotoxin. PQ (100 μM) potentiated IL-1 production (2–40 fold) and TNF production (2–18 fold). It is, therefore, possible that IL-1 and TNF are also involved in the pneumotoxic action of PQ.


Tumor Necrosis Tumor Necrosis Factor Mononuclear Cell Peripheral Blood Mononuclear Cell Healthy Donor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    R. D. Kimbrough and T. B. Gaines,Toxicity of paraquat to rats and its effect on rat lungs. Tox. App. Pharmacol.17, 679–690 (1970).Google Scholar
  2. [2]
    P. Smith, D. Heath and J. M. Kay,The pathogenesis and structure of paraquat-induced pulmonary fibrosis in rats. J. Pathol.114, 57–67 (1974).PubMedGoogle Scholar
  3. [3]
    G. M. Copland, A. Kolin and H. S. Shulman,Fatal pulmonary intra-alveolar fibrosis after paraquat ingestion. New Engl. J. Med.291, 290–292 (1974).PubMedGoogle Scholar
  4. [4]
    P. F. Piguet, M. A. Collart, G. E. Grau, Y. Kapanci and P. Vassalli,Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. J. Exp. Med.170, 655–663 (1989).PubMedGoogle Scholar
  5. [5]
    P. F. Piguet, M. A. Collart, G. E. Grau, A.-P. Sappino and P. Vassalli,Requirement of tumor necrosis factor for development of silica-induced pulmonary fibrosis. Nature344, 245–247 (1990).PubMedGoogle Scholar
  6. [6]
    C. A. Dinarello,Biology of interleukin 1. FASEB J.2, 108–115 (1988).PubMedGoogle Scholar
  7. [7]
    B. Beutler and A. Cerami,Cachectin: More than a tumor necrosis factor. New Engl. J. Med.316, 379–385 (1987).PubMedGoogle Scholar
  8. [8]
    B. J. Sugarman, B. B. Aggarwal, P. E. Hass, I. S. Figari, M. A. Palladino Jr. and H. M. Shepard,Recombinant human tumor necrosis factor-α: Effects on proliferation of normal and transformed cells in vitro. Science230, 943–945 (1985).PubMedGoogle Scholar
  9. [9]
    J. A. Schmidt, S. B. Mizel, D. Cohen and I. Green,Interleukin 1, a potential regulator of fibroblast proliferation. J. Immunol.128, 2177–2182 (1982).PubMedGoogle Scholar
  10. [10]
    J. A. Schmidt, C. N. Oliver, J. L. Lepe-Zuniga, I. Green and I. Gery,Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin 1. A potential role for interleukin 1 in the pathogenesis of silicosis. J. Clin. Invest.73, 1462–1472 (1984).PubMedGoogle Scholar
  11. [11]
    K. E. Stephens, A. Ishizaka, J. W. Larrick and T. A. Raffin,Tumor necrosis factor causes increased pulmonary perme-ability and edema. Comparison to septic acute lung injury. Am. Rev. Respir. Dis.137, 1364–1370 (1988).PubMedGoogle Scholar
  12. [12]
    A. Suwabe, K. Takahashi, S. Yasui, S. Arai and F. Sendo,Bleomycin-stimulated hamster alveolar macrophages release interleukin-1. Am. J. Pathol.132, 512–520 (1988).PubMedGoogle Scholar
  13. [13]
    P. J. Lisi, C. W. Chu, G. A. Koch, S. Endres, G. Lonnemann and C. A. Dinarello,Development and use of a radioimmunoassay for human interleukin-1 beta. Lymphokine Res.6, 229–244 (1987).PubMedGoogle Scholar
  14. [14]
    B. B. Aggarwal, W. J. Kohr, P. E. Hass, B. Moffat, S. A. Spencer, W. J. Henzel, T. S. Bringman, G. E. Nedwin, D. V. Goeddel and R. N. Harkins,Human tumor necrosis factor. Production, purification, and characterization. J. Biol. Chem.260, 2345–2354 (1985).PubMedGoogle Scholar
  15. [15]
    G. L. Plaa and H. Witschi,Chemicals, drugs, and lipid peroxidation. Ann. Rev. Pharmacol. Toxicol.16, 125–141 (1976).Google Scholar
  16. [16]
    G. Chaudhri and I. A. Clark,Reactive oxygen species facilitate the in vitro and in vivo lipopolysaccharide-induced release of tumor necrosis factor. J. Immunol.143, 1290–1294 (1989).PubMedGoogle Scholar
  17. [17]
    L. M. Colletti, D. G. Remick, G. D. Burtch, S. L. Kunkel, R. M. Strieter and D. A. Campbell Jr.,Role of tumor necrosis factor-α in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J. Clin. Invest.85, 1936–1943 (1990).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1992

Authors and Affiliations

  • A. Erroi
    • 1
  • M. Bianchi
    • 1
  • P. Ghezzi
    • 1
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

Personalised recommendations