The biological role of naturally-occurring cytokine inhibitors.
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.
Arend
W P
WP
Division of Rheumatology, University of Colorado Health Sciences Center, Denver 80262.
Malyak
M
M
Bigler
C F
CF
Smith
M F
MF
Janson
R W
RW
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
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