Skip to main content
SpringerLink
Log in

Effects of IL-1 muteins on cartilage degradation and as inducers of acute inflammation

  • Cytokines
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

IL-1 peptides with N-terminal amino acid mutations were cloned and expressed to help characterize structural requirements for activity. Addition of Thr-Asn to the N-terminus (DP516) or substitution of the first two residues (Ala-Pro) of mature, native IL-1β with Thr-Met (DuP118) had no effect on the potency of the muteins in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesisin vitro, or inducing mouse paw swellingin vivo. When Arg in position 4 of DuP118 was replaced by Glu (Glu-4), proteoglycan-synthesis-inhibitory activity was reduced to 20% and proteoglycan-degrading activity to 2% of that induced by native IL-1β. Glu-4 was much less active in inducing mouse paw swelling and gave maximal swelling about 40% that of native IL-1β. The data suggest that the presence of the positively charged side chain of Arg in position 4 may be important for the activity of IL-1 and may be useful in designing specific IL-1 receptor agonists/antagonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. D. D. Wood, E. J. Ihrie, C. A. Dinarello and P. L. Cohen,Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum.26, 975–983 (1983).

    PubMed  Google Scholar 

  2. J. J. Huang, R. C. Newton, K. Pezzella, M. Covington, T. Tamblyn, S. J. Rutledge, J. Gray, M. Kelley and Y. Lin,High-level expression in Escherichia coli of a soluble and fully active recombinant interleukin-1β. Mol. Biol. Med.4, 169–181 (1987).

    PubMed  Google Scholar 

  3. J. J. Huang, R. C. Newton, R. Horuk, J. B. Matthew, M. Covington, K. Pezzella and Y. Lin,Muteins of human interleukin-1 that show enhanced bioactivity. FEBS Letters223, 294–298 (1987).

    Article  PubMed  Google Scholar 

  4. E. C. Arner and M. A. Pratta,Independent effects of interleukin-1 on proteoglycan breakdown, proteoglycan synthesis, and prostaglandin E 2 release from cartilage in organ culture. Arthritis Rheum32, 288–297 (1989).

    PubMed  Google Scholar 

  5. G. Beck, G. S. Habicht, J. L. Benach and F. Miller,Interleukin-1, a common endogenous mediator of inflammation and the local Shwartzman reaction. J. Immunol.136, 3025–3031 (1986).

    PubMed  Google Scholar 

  6. C. A. Dinarello, J. G. Cannon, J. W. Mier, H. A. Bernheim, G. LoPreste, D. L. Lynn, R. N. Love, A. C. Webb, P. E. Auron, R. C. Reuben, A. Rich, S. M. Wolff and S. D. Putney,Multiple biological activities of human recombinant interleukin-1. J. Clin. Invest.77, 1734–1739 (1986).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. E.I. du Pont de Nemours & Company, Inc., 19880-0400, Wilmington, DE, USA

    M. A. Pratta, E. C. Arner, B. L. Rule & W. Galbraith

Authors
  1. M. A. Pratta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. C. Arner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. L. Rule
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Galbraith
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pratta, M.A., Arner, E.C., Rule, B.L. et al. Effects of IL-1 muteins on cartilage degradation and as inducers of acute inflammation. Agents and Actions 34, 60–62 (1991). https://doi.org/10.1007/BF01993238

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01993238

Keywords

Search

Navigation