Disease relevance of IL8

• IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes [1].
• A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL [1].
• ELR(+) CXC chemokines including IL-8 are known to be involved in the ischemia-reperfusion injuries in various organs including rodent brain [2].
• Genetically inactivated rotavirus was also effective for IL-8 induction, indicating that viral replication was not required [3].
• Secretion of IL-8 was dependent on an intact viral capsid, as single-shell particles were inert [3].

High impact information on IL8

• Transcytosis and surface presentation of IL-8 by venular endothelial cells [4].
• Previously, we demonstrated that IL-8 induces rapid mobilization of hematopoietic progenitor cells (HPC) from the bone marrow of rhesus monkeys [5].
• Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils [1].
• Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation [1].
• We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion [1].

Biological context of IL8

• Pure rhesus IL-8 was biologically active as measured by its ability to bind specifically to either rhesus (Kd = 0.5 nM) or human (Kd = 2 nM) IL-8 receptors and to promote in vitro chemotaxis of rhesus (EC50 = 2 nM) or human neutrophils (EC50 = 4 nM) [6].
• The open reading frame directs the translation of a 101 amino acid (aa) precursor, which is 94% identical to human IL-8 [6].
• Moreover, a mouse monoclonal antibody, DM/C7, which neutralizes human IL-8 activity, also recognized and neutralized (IC50 = 0.5-3.0 microgram/ml) rhesus IL-8 in vitro [6].
• A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred [1].
• In the healing experiment, stress decreased IL-8 and MIP-1alpha gene expression in both CeA lesioned and non-lesioned animals [7].

Anatomical context of IL8

• The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8) [1].
• Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP-1alpha gene expression during tissue healing in non-human primates [7].
• Rotavirus stimulates IL-8 secretion from cultured epithelial cells [3].
• Both cynomolgus receptors were functionally active in inducing guanosine 5'-O-(3-thio)triphosphate exchange on membranes in response to IL-8 and Gro-alpha and in mediating chemotactic activity of recombinant BA/F3 cells in response to IL-8 and Gro-alpha [8].
• Opioids were either incubated with monkey leukocytes or added directly to chemokines, and the number of cells migrating toward IL-8 (for neutrophils) or RANTES (for monocytes) was scored [9].

Associations of IL8 with chemical compounds

• Neutrophil recruitment in lipopolysaccharide-induced injury was associated with immunohistochemical localization of TNF-alpha, IL-1, and IL-8, whereas only TNF-alpha was consistently detected in DHR [10].
• Monkey neutrophils or monocytes were first treated with heptachlor, chlordane or toxaphene for 1 hour at 37 degrees C, and the number of cells migrating toward 200 ng/ml IL-8 (for neutrophils) or 100 ng/ml RANTES (for monocytes) were scored [11].
• The Duffy glycoprotein binds interleukin 8 [12].
• Dexamethasone and interleukin-10 treatment significantly reduced interleukin-1beta-induced uterine contractility (P <.05) and amniotic fluid prostaglandins (P <.05) but not interleukin-8 or interleukin-1 receptor antagonist [13].

Analytical, diagnostic and therapeutic context of IL8

• Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg) [1].
• Expression of E-selectin, P-selectin, VCAM-1, and ICAM-1 was assessed using immunohistochemistry and compared with leukocyte localization and immunohistochemical expression of interleukin (IL) 1, IL-8 and tumor necrosis factor-alpha (TNF-alpha) [10].
• The intact C terminus of IL-8, the molecule's "immobilization" domain, is required for the EC binding, transcytosis, and consequently, the in vivo proemigratory activity of IL-8, indicating that the described subcellular interactions of IL-8 with the ECs are functionally relevant [4].

References