Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Aug;39(8):1744–1747. doi: 10.1128/aac.39.8.1744

Interleukin-1 (IL-1)-induced resistance to bacterial infection: role of the type I IL-1 receptor.

M T Vogels 1, W M Eling 1, A Otten 1, J W van der Meer 1
PMCID: PMC162819  PMID: 7486912

Abstract

Pretreatment with a low dose of recombinant human interleukin-1 beta (IL-1) (3 to 30 micrograms/kg) 24 h before a lethal Pseudomonas aeruginosa infection prolongs survival in neutropenic mice. We investigated the role of the type I IL-1 receptor (IL-1RI) and IL-1RII in this IL-1-induced protection by using a specific IL-1 receptor antagonist (IL-1-Ra), which blocks effects mainly via IL-1RI. Pretreatment with IL-1Ra before IL-1 partially blocked the IL-1-induced enhanced survival, whereas pretreatment with a specific neutralizing monoclonal antibody to IL-1RI (35F5) eliminated the IL-1 induced protection. The nonapeptide fragment 163-171 of recombinant human IL-1 beta, which possesses the immunoadjuvant but not the inflammatory effect of the entire molecule via a non-receptor-mediated signal transduction process, did not reproduce the IL-1-induced protection. IL-1-induced protection was associated with reduced serum aspartate aminotransferase and alanine aminotransferase concentrations in conjunction with ameliorated histopathology of the liver. These findings may be due to reduced cytokine production and cytokine sensitivity of target cells after infection. We conclude that the IL-1-induced nonspecific resistance to infection is mediated by cells bearing IL-1RI and is associated with a reduction of liver damage.

Full Text

The Full Text of this article is available as a PDF (231.3 KB).

Selected References

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

  1. Arend W. P. Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest. 1991 Nov;88(5):1445–1451. doi: 10.1172/JCI115453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boraschi D., Ghiara P., Scapigliati G., Villa L., Sette A., Tagliabue A. Binding and internalization of the 163-171 fragment of human IL-1 beta. Cytokine. 1992 May;4(3):201–204. doi: 10.1016/1043-4666(92)90056-w. [DOI] [PubMed] [Google Scholar]
  3. Boraschi D., Nencioni L., Villa L., Censini S., Bossù P., Ghiara P., Presentini R., Perin F., Frasca D., Doria G. In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta. J Exp Med. 1988 Aug 1;168(2):675–686. doi: 10.1084/jem.168.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chizzonite R., Truitt T., Kilian P. L., Stern A. S., Nunes P., Parker K. P., Kaffka K. L., Chua A. O., Lugg D. K., Gubler U. Two high-affinity interleukin 1 receptors represent separate gene products. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8029–8033. doi: 10.1073/pnas.86.20.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gayle M. A., Sims J. E., Dower S. K., Slack J. L. Monoclonal antibody 1994-01 (also known as ALVA 42) reported to recognize type II IL-1 receptor is specific for HLA-DR alpha and beta chains. Cytokine. 1994 Jan;6(1):83–86. doi: 10.1016/1043-4666(94)90012-4. [DOI] [PubMed] [Google Scholar]
  6. Margulis B. A., Sandler S., Eizirik D. L., Welsh N., Welsh M. Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function. Diabetes. 1991 Nov;40(11):1418–1422. doi: 10.2337/diab.40.11.1418. [DOI] [PubMed] [Google Scholar]
  7. Martel-Pelletier J., McCollum R., Pelletier J. P. The synthesis of IL-1 receptor antagonist (IL-1ra) by synovial fibroblasts is markedly increased by the cytokines TNF-alpha and IL-1. Biochim Biophys Acta. 1993 Feb 17;1175(3):302–305. doi: 10.1016/0167-4889(93)90221-a. [DOI] [PubMed] [Google Scholar]
  8. McIntyre K. W., Stepan G. J., Kolinsky K. D., Benjamin W. R., Plocinski J. M., Kaffka K. L., Campen C. A., Chizzonite R. A., Kilian P. L. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med. 1991 Apr 1;173(4):931–939. doi: 10.1084/jem.173.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McMahan C. J., Slack J. L., Mosley B., Cosman D., Lupton S. D., Brunton L. L., Grubin C. E., Wignall J. M., Jenkins N. A., Brannan C. I. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 1991 Oct;10(10):2821–2832. doi: 10.1002/j.1460-2075.1991.tb07831.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Neta R., Vogel S. N., Plocinski J. M., Tare N. S., Benjamin W., Chizzonite R., Pilcher M. In vivo modulation with anti-interleukin-1 (IL-1) receptor (p80) antibody 35F5 of the response to IL-1. The relationship of radioprotection, colony-stimulating factor, and IL-6. Blood. 1990 Jul 1;76(1):57–62. [PubMed] [Google Scholar]
  11. Ono M., Kohda H., Kawaguchi T., Ohhira M., Sekiya C., Namiki M., Takeyasu A., Taniguchi N. Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-1 and interleukin-6 in human hepatoma cells. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1100–1107. doi: 10.1016/0006-291x(92)91845-h. [DOI] [PubMed] [Google Scholar]
  12. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. doi: 10.1038/bjc.1977.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Renić M., Culo F., Bilić A., Bukovec Z., Sabolović D., Zupanović Z. The effect of interleukin 1 alpha on acetaminophen-induced hepatotoxicity. Cytokine. 1993 May;5(3):192–197. doi: 10.1016/1043-4666(93)90004-o. [DOI] [PubMed] [Google Scholar]
  14. Sims J. E., Acres R. B., Grubin C. E., McMahan C. J., Wignall J. M., March C. J., Dower S. K. Cloning the interleukin 1 receptor from human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8946–8950. doi: 10.1073/pnas.86.22.8946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sims J. E., Gayle M. A., Slack J. L., Alderson M. R., Bird T. A., Giri J. G., Colotta F., Re F., Mantovani A., Shanebeck K. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6155–6159. doi: 10.1073/pnas.90.13.6155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tagliabue A., Antoni G., Boraschi D. Defining agonist peptides of human interleukin-1 beta. Lymphokine Res. 1989 Fall;8(3):311–315. [PubMed] [Google Scholar]
  17. Vogels M. T., Cantoni L., Carelli M., Sironi M., Ghezzi P., van der Meer J. W. Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice. Antimicrob Agents Chemother. 1993 Dec;37(12):2527–2533. doi: 10.1128/aac.37.12.2527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vogels M. T., Hermsen C. C., Huys H. L., Eling W. M., van der Meer J. W. Roles of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, platelet-activating factor, and arachidonic acid metabolites in interleukin-1-induced resistance to infection in neutropenic mice. Infect Immun. 1994 May;62(5):2065–2070. doi: 10.1128/iai.62.5.2065-2070.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vogels M. T., Lindley I. J., Curfs J. H., Eling W. M., van der Meer J. W. Effects of interleukin-8 on nonspecific resistance to infection in neutropenic and normal mice. Antimicrob Agents Chemother. 1993 Feb;37(2):276–280. doi: 10.1128/aac.37.2.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vogels M. T., Mensink E. J., Ye K., Boerman O. C., Verschueren C. M., Dinarello C. A., van der Meer J. W. Differential gene expression for IL-1 receptor antagonist, IL-1, and TNF receptors and IL-1 and TNF synthesis may explain IL-1-induced resistance to infection. J Immunol. 1994 Dec 15;153(12):5772–5780. [PubMed] [Google Scholar]
  21. Vogels M. T., Sweep C. G., Hermus A. R., van der Meer J. W. Interleukin-1-induced nonspecific resistance to bacterial infection in mice is not mediated by glucocorticosteroids. Antimicrob Agents Chemother. 1992 Dec;36(12):2785–2789. doi: 10.1128/aac.36.12.2785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vogels M. T., van der Meer J. W. Use of immune modulators in nonspecific therapy of bacterial infections. Antimicrob Agents Chemother. 1992 Jan;36(1):1–5. doi: 10.1128/aac.36.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wallach D., Holtmann H., Engelmann H., Nophar Y. Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1. J Immunol. 1988 May 1;140(9):2994–2999. [PubMed] [Google Scholar]
  24. van der Meer J. W., Barza M., Wolff S. M., Dinarello C. A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. van der Meer J. W. The effects of recombinant interleukin-1 and recombinant tumor necrosis factor on non-specific resistance to infection. Biotherapy. 1988;1(1):19–25. doi: 10.1007/BF02170132. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES