Recent Advances in Immunopathophysiology of Interleukin-6: An Innovative Therapeutic Drug, Tocilizumab (Recombinant Humanized Anti-human Interleukin-6 Receptor Antibody), Unveils The Mysterious Etiology of Immune-Mediated Inflammatory Diseases

Abstract

Interleukin (IL)-6 cDNA was originally cloned as a terminal B cell differentiation factor into antibody-producing plasma cells. This revealed that it is a multifunctional cytokine that acts on a variety of cells. From the clinical viewpoint, it is especially important that IL-6 acts on hepatocytes to induce acute-phase reactants, including C-reactive protein, serum amyloid A protein, and fibrinogen, and to decrease serum albumin levels. Very recently, this cytokine has been found to enhance the synthesis of a peptide called hepcidin in the liver which regulates iron recycling, resulting in anemia due to hypofferemia. It has also been shown that IL-6 is responsible for various clinical symptoms, including the appearance of autoantibodies, fatigue, anemia, anorexia, fever, and increases in the erythrocyte sedimentation rate, all of which develop in patients with various chronic autoimmune inflammatory diseases. In practice, blocking the IL-6 signaling pathway with a recombinant humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), has dramatically improved all the signs and symptoms of these patients. A study in mice demonstrated that IL-6 promotes the development of a new type of T-helper cells called Th17 cells that impact the pathogenesis of autoimmune diseases. This suggests that TCZ is not only an antiinflammatory agent but also might affect basic autoimmunity. In this review, recent advances in the immunobiology of interleukin-6 related to immune-mediated diseases are discussed.

Prognostic Role of Platelet to Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis

“…Indeed, we found the strongest association between PLR and survival in metastatic or mixed groups of patients when compared with study populations with locoregional disease. Although a variety of cytokines are implicated in the systemic inflammatory response, IL6 acts to increase the synthesis of acute phase proteins, including CRP, and to decrease albumin production in the liver, the two elements encompassed by the GPS (20). IL6 also stimulates the differentiation of megakaryocytes to platelets and is involved in recruitment of neutrophils (21,22).…”

The Influence of Excessive IL-6 Production In Vivo on the Development and Function of Foxp3+ Regulatory T Cells

“…IL-6 also activates nonimmune cells such as endothelial cells to induce the production of adhesion molecules and chemoattractants. In addition, local production of IL-6 results in the elevation of circulating IL-6 levels, which in turn induces systemic acute phase responses including the synthesis of C reactive protein, serum amyloid A, and fibrinogen in the liver (2,3). Thus, IL-6 regulates various aspects of inflammatory responses both locally and systemically.…”

A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke

“…Biologics are increasingly being developed for chronic diseases, such as tumour necrosis factor (TNF)-a antibodies and receptor antagonists in arthritis [16][17][18], and anti-immunoglobulin (Ig)E antibodies in asthma [19]. Moreover, antibody trials on COPD are also underway that target IL-1b (canakinumab) [20].…”