Interleukin-6: structure-function relationships

Protein Sci. 1997 May;6(5):929-55. doi: 10.1002/pro.5560060501.


Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry*
  • Antigens, CD / physiology*
  • Arthritis, Rheumatoid / immunology
  • Castleman Disease / immunology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7
  • Cytokines / physiology
  • Female
  • Growth Hormone / chemistry
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / chemistry*
  • Interleukin-6 / physiology*
  • Models, Biological
  • Models, Structural
  • Molecular Sequence Data
  • Multiple Myeloma / immunology
  • Osteoporosis, Postmenopausal / immunology
  • Protein Structure, Secondary*
  • Psoriasis / immunology
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-6
  • Receptors, Somatotropin / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Antigens, CD
  • Cytokines
  • Interleukin-6
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Receptors, Somatotropin
  • Growth Hormone

Associated data

  • GENBANK/D13227
  • GENBANK/L26028
  • GENBANK/L26032
  • GENBANK/L34165
  • GENBANK/L46802
  • GENBANK/L46803
  • GENBANK/L46804
  • GENBANK/M24221
  • GENBANK/M26744
  • GENBANK/M80258
  • GENBANK/U12234
  • GENBANK/X57317
  • GENBANK/X68723
  • GENBANK/Y00081