Sequential generation of cytokines during the initiative phase of inflammation, with reference to neutrophils

Abstract

Studies have suggested the role of cytokines in inflammation, as determined by results obtained in vitro, or with assessments of clinical samples. However, extrapolation of in vitro results to an in vivo situation must be made with caution, and findings obtained from clinical samples tend to lack a causal relation between cytokines and inflammatory responses. Animal models of inflammation can be useful in understanding roles of cytokines at sites of inflammation. We examined the production kinetics and cellular sources of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra), and obtained evidence for the involvement of these cytokines in a rabbit model of arthritis induced by lipopolysaccharide (LPS). We also attempted to analyze the inflammatory cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1Ra. Understanding the role of cytokines in animal models paves the way to a better understanding of disease in humans.

Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

“…This is in accordance with findings about lipopolysaccharide-induced arthritis, which showed that synovial IL-8 levels were not affected by a depletion of neutrophils (11). Besides this, and maybe of minor importance, there was even a small increase in CSF IL-8 levels in fucoidin-treated rabbits, but whether such an increase is part of a higher local chemotactic signal trying to induce pleocytosis remains to be clarified.…”

IL-1 Receptor-Associated Kinase and Low Molecular Weight GTPase RhoA Signal Molecules Are Required for Bacterial Lipopolysaccharide-Induced Cytokine Gene Transcription

“…LPS stimulates the synthesis and release of proinflammatory cytokines such as IL-1, TNF, IL-1, IL-6, and IL-8 from monocytes and macrophages. These cytokines can further activate monocytes, neutrophils, and lymphocytes, initiating cellular injury and tissue damage (1,2).…”

Big roles for small GTPases in the control of directed cell movement

“…cAMP induces its own production and secretion by binding and activating cAR1 (cAMP receptor 1) and cAR3, which then promote the activation of the cAMP-synthesizing enzyme adenylate cyclase. Several observations suggest that signal relay also occurs in chemotactic neutrophils, representing a potential mechanism which they use to attract a greater number of leucocytes to sites of inflammation [18][19][20].…”