(88) found that IL-2 upregulates the expression of IL-12 and increases the response of NK to IL-12

(88) found that IL-2 upregulates the expression of IL-12 and increases the response of NK to IL-12. permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in Mouse monoclonal to OTX2 inducing the sensorineumral hearing loss in otitis media should be pursued. pathway, whereas the pathway is activated by the lipopolysaccharide (LPS) portion of endotoxin and other nonprotein agents. C3 is biologically inactive, but cleavage by C3 convertase yields active fragments including C3a and C3b. Deposition of the active (+) PD 128907 cleavage product C3b on the surface of foreign particles or target cells allows recognition by receptors on phagocytic cells. C3a is a potent activator of mast cells and basophils and leads to release of histamine from secretory granules. Proteolytic cleavage of C5 occurs via both pathways and generates C5a, a potent mediator of inflammation. C5a is the major complement-derived chemotactic agent for neutrophils, eosinophils, monocytes, and macrophages. C5a also has the ability to activate platelets, leading to their aggregation and surface expression of P-selectin. Complement activation has been observed in human middle ear effusion by some authors (8, 9). In animal models of acute otitis media (AOM), animals were treated with cobra venom to deplete complement and then their middle ears were antigenically challenged (10). Complement-depleted animals had (+) PD 128907 significantly less inflammation and decreased volume of effusion when compared to controls. Middle ear mucosa from children with chronic otitis media (COM) with effusion has shown large amounts of complement fragments C3 and C9 when analyzed by immunofluorescence microscopy (11). In humans, deficiencies of the complement system are known to cause recurrent or COM (12). Despite this fact, it appears that complement itself may be harmful to the middle ear mucosa. Membrane cofactor protein (MCP) and protectin (CD59) are two middle ear proteins which help prevent unrestricted complement damage (11). Cytokines Cytokines are glycoproteins, produced by inflammatory cells and epithelial cells, which modulate the immune response. Cytokines extensively conduct inter-cell communication. Inflammatory cells including neutrophils, macrophages, and lymphocytes use cytokines to coordinate all stages of the inflammatory response. Production of cytokines is conducted by a wide variety of cell types. For example, IL-1 is produced and secreted by macrophages, lymphocytes, vascular endothelial cells, neutrophils, fibroblasts, and monocytes. There are many biological effects including: chemotaxis of cytotoxic T-cells and B-lymphocytes, cytokine synthesis of IL-2 and IL-8 and TNF, neutrophil chemotaxis and (+) PD 128907 degranulation, fibroblast and epithelial proliferation, and histamine release (13, 14). The present theory is that cytokines are responsible for many of the inflammatory changes induced by pathogenic organisms during OM (15). Different cytokines are involved in the early and late stages of inflammation and it has been observed in a bilateral study of effusion that cytokine production and concentration can vary between the ears (16). IL-1 and TNF- are early-response cytokines with IL-1 being a more potent activator than TNF- (17). IL-1 may be more important than TNF- in the elicitation stage of inflammation, while there is more of a need for TNF- during recruitment and maintenance stages (18, 19). IL-1 and TNF- from macrophages induce the expression of glycoprotein adhesion molecules on the surface of vascular endothelial cells which bind leukocytes so they can leave the circulation and enter the site of infection. IL-1 IL-1 was originally identified as a lymphokine that was mitogenic for murine thymocytes (20). Now IL-1 is known to be produced by many different cells to regulate immune responses (21). IL-1 is one of the most active substances inducing bone resorption through osteoclast activation (22). This IL-1-mediated bone destruction is one of the clinical characteristics that signal the onset of chronic OM. Neutrophils are a major producer of IL-1. IL-1 induces the production of IL-1 in neutrophils in a positive-feedback mechanism (23). IL-1 has been shown to stimulate the synthesis of TNF, IL-2, IL-6, and IL-8 (24-27). IL-1 is comprised of two principal 17kDa polypeptides, IL-1 and IL-1. Genes found on chromosome 2 encode these two molecular species (28). They have the same biological activities and bind to the same receptor on cell.