title: The biological role of naturally-occurring cytokine inhibitors.
abstract: Four different mechanisms of cytokine inhibition might be involved in regulation of cytokine effects in vivo. Different cytokines may exhibit opposing biological effects on a specific target cell or in a particular disease. Autoantibodies to cytokines may block cytokine effects in vivo or may function as carriers to deliver cytokines to tissues. Soluble receptors of cytokines, particularly for IL-2 and TNF alpha, may be released by cell activation. Lastly, a specific receptor antagonist of IL-1, IL-1ra, is synthesized by human monocytes and macrophages, particularly under the influence of GM-CSF. IL-1ra is the first described naturally-occurring receptor antagonist of any cytokine or hormone-like molecule. It is not yet known whether IL-1ra is produced in tissues in human diseases as an endogenous anti-inflammatory factor. Whether any of these potential mechanisms to regulate cytokine effects will be of value in the treatment of human diseases remains to be determined.
authors.affiliation: Division of Rheumatology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: W P
authors.initials: WP
authors.lastname: Arend
authors.forename: M
authors.initials: M
authors.lastname: Malyak
authors.forename: C F
authors.initials: CF
authors.lastname: Bigler
authors.forename: M F
authors.initials: MF
authors.lastname: Smith
authors.forename: R W
authors.initials: RW
authors.lastname: Janson
mesh_terms: D001323:Autoantibodies / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D011506:Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins
chemical_list: D001323:Autoantibodies; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins