Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte Recruitment

Abstract

IL-6-/- mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6-/- leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC). EC express only the gp130 signal transducing chain and not the subunit-specific IL-6R and are therefore unresponsive to IL-6. However, EC are responsive to a combination of IL-6 and soluble IL-6R as measured by the activation of STAT3, chemokine expression, and augmentation of ICAM-1. Activation by IL-6-IL-6R complexes was inhibited by an IL-6 receptor antagonist and potentiated by a superagonist. Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.

IL-6 promoter polymorphisms in rheumatoid arthritis

“…While an overall normal inflammatory response, paralleled with three-fold higher TNF␣ levels, 24 resulted in IL-6 −/− mice after a systemic stimulus (LPS), an impaired response in these mice was observed when a local stimulus (turpentine) was used. 24,25 This is consistent with in vitro and in vivo evidence supporting the concept that the IL-6 system plays a sensitive role in local inflammatory reactions by amplifying leukocyte recruitment 26 and with the capacity of IL-6 to protect against LPS toxicity. 9,27 In summary, the data from the present study indicate that the IL-6 promoter polymorphisms studied do not play a major role as genetic susceptibility factors for RA.…”

Inflammatory Response and Glutathione Peroxidase in a Model of Stroke

“…Levels of IL-6 had a strong correlation with neurologic function and infarct size in animal experimental ischemia as well as in stroke patients (33,34). It was also demonstrated that the IL-6 system plays an important role in local inflammatory reactions by amplifying leukocyte recruitment and changing endothelial permeability (35). The ability of GPx1 to modulate the level of IL-6 is most likely due to the inhibitory effect on ROS production, which is known by several investigators to stimulate transcriptional activation of IL-6 (36,37).…”

Targeting the interleukin‐6 receptor: A new treatment for systemic juvenile idiopathic arthritis?

“…Indeed, IL-6 induces endothelial expression of adhesion molecules and endothelial production of monocyte chemoattractant protein 1 (58), a chemokine responsible for monocyte recruitment. Moreover, IL-6 Ϫ/Ϫ mice show impaired leukocyte accumulation at the site of inflammation (58) and defective transition to a chronic mononuclear cell infiltrate (59). IL-6 is also involved in the recruitment of mesenchymal vascular cells and neoangiogenesis in vivo (60), and has been shown to induce proliferation of synovial fibroblasts (61).…”