The Pathophysiologic Roles of Interleukin-6 in Human Disease

  title={The Pathophysiologic Roles of Interleukin-6 in Human Disease},
  author={Dimitris A. Papanicolaou and Ronald L. Wilder and Stavros C. Manolagas and George P. Chrousos},
  journal={Annals of Internal Medicine},
Dr. Dimitris A. Papanicolaou (Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health [NIH], Bethesda, Maryland): During inflammation, the inflammatory cytokines tumor necrosis factor-, interleukin-1, and interleukin-6 are secreted, in that order [1, 2]. Interleukin-6 then inhibits the secretion of tumor necrosis factor- and interleukin-1 [3], activates the production of acute-phase reactants from the liver [4], and stimulates… 

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The polymorphisms of the two inflammatory cytokines, IL-1 and IL-10, are described and their significance in various diseases of autoimmune or inflammatory nature is described.

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A humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown to be an effective treatment in several large phase III clinical trials in RA with rapid and sustained improvement in disease activity, reducing radiographic joint damage and improving physical function.

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    Annals of the New York Academy of Sciences
  • 1999
On the basis of a more complete understanding of macrophage effector and immunoregulatory activities, new hopes arise from the possible development of more sophisticated antimacrophage treatments for the management of autoimmune rheumatic diseases.

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Human intestinal epithelial and smooth muscle cells are potent producers of IL-6.

The profound response to IL-1beta and TNF-alpha stimulation by both cell lines suggests that human intestinal parenchymal cells, influenced by paracrine mediators liberated from proinflammatory cells, might significantly contribute to the overall systemic inflammatory response by producing IL-6.

Effect of catecholamines on intracellular cytokine synthesis in human monocytes.

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In the tumor microenvironment coexisting with Hashimoto's thyroiditis (HT), cytokines secreted by the tumor cells, stroma cells, or immune cells play a critical role in the regulation of tumor



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Interleukin-6 family of cytokines and gp130.

It is shown that IL-6, together with IL-3, induces the expansion of murine hematopoietic progenitor cells and to be responsible for stimulating resting cells to enter the Cl-phase, a fact that may explain the redundant activities of IL- 6 and LIF.

Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis.

Iliac bone marrow may be an important site for the production or accumulation of IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in patients with polyarthritis.

Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice.

The similarity of these findings to those of multicentric Castleman's disease, taken together with the observation that lymph nodes from these patients elaborate large amounts of this cytokine, suggest that the inappropriate synthesis of IL-6 has a primary role in the pathogenesis of this systemic lymphoproliferative disorder.

Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides.

There is a significant correlation between serum IL-6 activity and serum levels of C-reactive protein, alpha 1-acid glycoprotein,alpha 1-antitrypsin, fibrinogen, and haptoglobin, which indicates that IL- 6 is related to disease activity in patients with RA.

IgG1 plasmacytosis in interleukin 6 transgenic mice.

The evidence indicates that deregulated gene expression of IL-6 can trigger polyclonal plasmacytosis but cannot induce plasmACYtoma, and it is suggested that additional genetic changes may be required for the generation of plasma cell neoplasia.

Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness.

The low T3 syndrome in nonthyroidial illness is associated with high serum IL-6 levels, and even when IL- 6 is assumed to play a causative role, the variation of serum T3 in NTI-patients remains largely unexplained.

The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL- 6 and prolongation of the plasma half-life of IL-6

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Interleukin-6 mediates host defense responses induced by abdominal surgery.

It is concluded that abdominal surgery causes acute release of IL-6, but not TNF, in the portal circulation, andIL-6 seems to be a major endogenous mediator of fever and the acute-phase response.