Proinflammatory cytokine responses

LPS Priming Potentiates and Prolongs DON-induced Proinflammatory Cytokine Responses... 

Islam, Z. and Pestka J.J. LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse. Toxicol. Appl. Pharmacol. 211,53, 2005. 

Respiratory syncytial virus (RSV) infection is a major cause of bronchiolitis in infants, whereas influenza A infection usually manifests as an upper respiratory tract infection. The immunological responses of infants to RSV infection and influenza A infection are different. In our studies of the cytokine responses during these infections, we found that the serum concentrations of IL-4, IL-5, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) in infants with RSV infection were significantly higher than those with influenza A infection (S8). The concentration of TNF-a in nasopharyngeal aspirates was significantly lower in infants with RSV infection. Therefore, a predominant T helper cell type 2 (Th2) cytokine and related immunological response was observed in infants with RSV infection, whereas a predominantly proinflammatory cytokine response was observed in infants with influenza A infection. This may explain the different clinical manifestations of the two viral infections in infants (S8). 

Iwagaki, A., Porro, M., Pollack, M. Influence of synthetic antiendotoxin peptides on lipopolysaccharide (LPS) recognition and LPS-induced proinflammatory cytokine responses by cells expressing membrane-bound CD14. Infect Immun 68 (2000) 1655-1663. 

Kube D, Sontich U, Fletcher D, Davis PB. Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithehal cell lines. Am J Physiol Lung Cell Mol Physiol 2001 280 L493. 

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

TNF is a pleiotropic cytokine exerting a wide range of cellular responses, that affect biological processes such as lipid metabolism, coagulation, and insulin resistance and the function of endothelial cells. As a major proinflammatory cytokine TNF is also involved in progression of diseases like cancer, Alzheimer, Diabetes type II, cardiovascular, pulmonary or neurological disorders, and many autoimmune diseases. Blocking the action of TNF clearly reduces its inflammatory potential on various autoimmune disorders like Crohn s disease, rheumatoid arthritis (RA), and psoriasis. 

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

The adjunctive agent dexamethasone has been shown to improve outcomes in selected patient populations with meningitis. Dexamethasone inhibits the release of proinflammatory cytokines and limits the CNS inflammatory response stimulated by infection and antibiotic therapy. 

Jung, H.C., Eckmann, L., Yang, S.K, Panja, A., Fierer, J., Morzyckawroblewska, E. and Kagnoff, M.F. (1995) A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. Journal of Clinical Investigation 95, 55-65. 

---