Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow

Abstract

Recombinant human interleukin-6 (IL-6) causes both a thrombocytosis and leukocytosis. The thrombocytosis is caused by an accelerating thrombocytopoiesis, but the mechanism of the leukocytosis is unknown. This study was designed to determine the relative contributions of marrow stimulation and intravascular demargination to the IL-6 induced neutrophilia. IL-6 (2 microgram/kg), administered intravenously to rabbits, caused a biphasic neutrophilia with an initial peak at 3 h and a second peak at 9 h. Using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) to label dividing polymorphonuclear leukocytes (PMNs) in the bone marrow, we showed that IL-6 treatment mobilizes PMNs from the marginated pool into the circulating pool at 2-6 h with a decrease in L-selectin expression on PMNs and also accelerates the release of PMNs from the postmitotic pool in the bone marrow at 12-24 h. We have concluded that IL-6 causes a biphasic neutrophilia wherein the first peak results from the mobilization of PMNs into the circulating pool from the marginated pool and the second peak results from an accelerated bone marrow release of PMNs.

Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters

“…IL-6 is considered an important multifunctional cytokine involved in the regulation of a variety of cellular responses, including the induction of acute-phase protein synthesis, lymphocyte activation and haematopoiesis [48]. It has been shown previously that IL-6 is a potent stimulator of the bone marrow that increases the transit of PMN and monocytes through the marrow and their release into the circulation [49]. IL-6 also promotes the sequestration of PMN in the lung [50] in a similar manner to that of IL-8 [51].…”

Hind limb perconditioning renoprotection by modulation of inflammatory cytokines after renal ischemia/reperfusion

“…10 The protective effect of limb remote conditioning in lung injury after pulmonary resection was associated by decreased serum level of TNF-a and IL-6 in a randomized control trial study by Li et al 22 Taken together, these studies support a possible role for TNF-a in short-time ischemic conditioning treatment. IL-6 which is released by macrophages in the site of ischemia increases renal inflammation by recruiting more neutrophils into the injured kidney, stimulation of neutrophil release from the bone marrow, 23 prevention of neutrophil apoptosis and activation of neutrophils to produce toxic enzymes. 24 In our study, increased IL-6 expression in the renal tissues, 24 h after reperfusion is consistent with the previous reports.…”

Targeting Interleukin-6 in Rheumatoid Arthritis

“…Neutropenia largely due to migration of neutrophils [70] was commonly reported in patients treated with tocilizumab. Generally, this was not associated with an increased risk of infections.…”