Skip to main content
Immunology logoLink to Immunology
. 1997 Jun;91(2):193–196. doi: 10.1046/j.1365-2567.1997.00252.x

Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta IL-10 by human leucocytes.

A M van Furth 1, E M Verhard-Seijmonsbergen 1, R van Furth 1, J A Langermans 1
PMCID: PMC1363846  PMID: 9227316

Abstract

The present study concerns the effect of the xanthine derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL-10) by human leucocytes during stimulation with lipopolysaccharide (LPS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimulated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae was inhibited by both drugs. The production of IL-10 by leucocytes stimulated with LPS and Hib was inhibited by both xanthine derivates only at 48 hr. However, incubation of leucocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four- and twofold at 24 hr and 48 hr, respectively. In all instances, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.

Full text

PDF
193

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bursten S., Weeks R., West J., Le T., Wilson T., Porubek D., Bianco J. A., Singer J. W., Rice G. C. Potential role for phosphatidic acid in mediating the inflammatory responses to TNF alpha and IL-1 beta. Circ Shock. 1994 Sep;44(1):14–29. [PubMed] [Google Scholar]
  2. Cassatella M. A. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995 Jan;16(1):21–26. doi: 10.1016/0167-5699(95)80066-2. [DOI] [PubMed] [Google Scholar]
  3. Dubravec D. B., Spriggs D. R., Mannick J. A., Rodrick M. L. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6758–6761. doi: 10.1073/pnas.87.17.6758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Endres S. Messengers and mediators: interactions among lipids, eicosanoids, and cytokines. Am J Clin Nutr. 1993 May;57(5 Suppl):798S–800S. doi: 10.1093/ajcn/57.5.798S. [DOI] [PubMed] [Google Scholar]
  5. Han J., Thompson P., Beutler B. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J Exp Med. 1990 Jul 1;172(1):391–394. doi: 10.1084/jem.172.1.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
  7. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  8. Kuhns D. B., Alvord W. G., Gallin J. I. Increased circulating cytokines, cytokine antagonists, and E-selectin after intravenous administration of endotoxin in humans. J Infect Dis. 1995 Jan;171(1):145–152. doi: 10.1093/infdis/171.1.145. [DOI] [PubMed] [Google Scholar]
  9. Meisel C., Vogt K., Platzer C., Randow F., Liebenthal C., Volk H. D. Differential regulation of monocytic tumor necrosis factor-alpha and interleukin-10 expression. Eur J Immunol. 1996 Jul;26(7):1580–1586. doi: 10.1002/eji.1830260726. [DOI] [PubMed] [Google Scholar]
  10. Neuner P., Klosner G., Schauer E., Pourmojib M., Macheiner W., Grünwald C., Knobler R., Schwarz A., Luger T. A., Schwarz T. Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells. Immunology. 1994 Oct;83(2):262–267. [PMC free article] [PubMed] [Google Scholar]
  11. Platzer C., Meisel C., Vogt K., Platzer M., Volk H. D. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol. 1995 Apr;7(4):517–523. doi: 10.1093/intimm/7.4.517. [DOI] [PubMed] [Google Scholar]
  12. Rice G. C., Brown P. A., Nelson R. J., Bianco J. A., Singer J. W., Bursten S. Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3857–3861. doi: 10.1073/pnas.91.9.3857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schandené L., Vandenbussche P., Crusiaux A., Alègre M. L., Abramowicz D., Dupont E., Content J., Goldman M. Differential effects of pentoxifylline on the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells. Immunology. 1992 May;76(1):30–34. [PMC free article] [PubMed] [Google Scholar]
  14. Semmler J., Gebert U., Eisenhut T., Moeller J., Schönharting M. M., Alléra A., Endres S. Xanthine derivatives: comparison between suppression of tumour necrosis factor-alpha production and inhibition of cAMP phosphodiesterase activity. Immunology. 1993 Apr;78(4):520–525. [PMC free article] [PubMed] [Google Scholar]
  15. Strieter R. M., Remick D. G., Ward P. A., Spengler R. N., Lynch J. P., 3rd, Larrick J., Kunkel S. L. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1230–1236. doi: 10.1016/s0006-291x(88)81271-3. [DOI] [PubMed] [Google Scholar]
  16. Sáez-Llorens X., Ramilo O., Mustafa M. M., Mertsola J., de Alba C., Hansen E., McCracken G. H., Jr Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. Antimicrob Agents Chemother. 1990 May;34(5):837–843. doi: 10.1128/aac.34.5.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Westendorp R. G., Langermans J. A., Huizinga T. W., Elouali A. H., Verweij C. L., Boomsma D. I., Vandenbroucke J. P., Vandenbrouke J. P. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997 Jan 18;349(9046):170–173. doi: 10.1016/s0140-6736(96)06413-6. [DOI] [PubMed] [Google Scholar]
  18. van Deventer S. J., Büller H. R., ten Cate J. W., Aarden L. A., Hack C. E., Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. 1990 Dec 15;76(12):2520–2526. [PubMed] [Google Scholar]
  19. van Furth A. M., Seijmonsbergen E. M., Langermans J. A., van der Meide P. H., van Furth R. Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae-stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes. Clin Diagn Lab Immunol. 1995 Nov;2(6):689–692. doi: 10.1128/cdli.2.6.689-692.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. van Furth A. M., Steenwijk T. M., Langermans J. A., van Furth R. In vitro effect of dexamethasone, pentoxifylline, and anti-endotoxin monoclonal antibody on the release of proinflammatory mediators by human leukocytes stimulated with Haemophilus influenzae type B. Pediatr Res. 1994 Jun;35(6):725–728. doi: 10.1203/00006450-199406000-00020. [DOI] [PubMed] [Google Scholar]
  21. van der Poll T., Jansen J., Levi M., ten Cate H., ten Cate J. W., van Deventer S. J. Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees. J Exp Med. 1994 Nov 1;180(5):1985–1988. doi: 10.1084/jem.180.5.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. von der Möhlen M. A., Kimmings A. N., Wedel N. I., Mevissen M. L., Jansen J., Friedmann N., Lorenz T. J., Nelson B. J., White M. L., Bauer R. Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. J Infect Dis. 1995 Jul;172(1):144–151. doi: 10.1093/infdis/172.1.144. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES