Publisher Summary This chapter focuses on structure and expression of interleukin-6 (IL-6), which is a cytokine with pleiotropic activities that plays a central role in host defense. IL-6 can exert growth-inducing, growth-inhibitory, and differentiation-inducing activities, depending on the target cells. These activities include (1) terminal differentiation (secretion of immunoglobulins) in B cells and (2) growth promotion on various B cells. IL-6 has been implicated in the pathology of many diseases including multiple myeloma, mesangial proliferative glomerulonephritis, rheumatoid arthritis, and acquired immunodeficiency syndrome (AIDS). Selective inhibition of the synthesis or of the action of IL-6 may have therapeutic benefit against the IL-6-associated diseases. On the other hand, IL-6 has potent antitumor activity against certain types of tumors. Application of IL-6 is promising in cancer treatment as well as in treatment of radiation- or chemotherapy-induced myelosuppression. The cell biology of the intracellular events that link transduction to gene regulation is an important area, and work on these topics helps to understand such phenomena as multifunction of IL-6 and bidirectional effects of cell growth depending on the cell type.

Interleukin-6 in biology and medicine

A review of premature birth and subclinical infection

Haemopoietic receptors and helical cytokines

Acute respiratory distress syndrome (ARDS) involves an intense inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta, and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.164.10.2104013

Cytokine balance in the lungs of patients with acute respiratory distress syndrome.

https://www.cell.com/neuron/pdf/0896-6273(91)90258-2.pdf

Neuropoietic cytokines in the hematopoietic fold

Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection.

An enzyme-linked immunosorbent assay for the measurement of human interleukin-6.

Establishment of strongly neutralizing monoclonal antibody to human interleukin-6 and its epitope analysis.

Detection of monocyte chemotactic and activating factor (MCAF) in normal blood and urine using a sensitive ELISA

An anti human interleukin-6 monoclonal antibody, which has a high specificity, as well as a hybridoma producing the same is disclosed. Not more than 4 ng of the monoclonal antibody can reduce the biological activity of 200 pg of human interleukin-6 by 50%.

Shingou Sakurai

Papers

Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection.

An enzyme-linked immunosorbent assay for the measurement of human interleukin-6.

Establishment of strongly neutralizing monoclonal antibody to human interleukin-6 and its epitope analysis.

Detection of monocyte chemotactic and activating factor (MCAF) in normal blood and urine using a sensitive ELISA

Anti-human interleukin-6 monoclonal antibody