Interleukin-1 and

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Kim MO, Suh HS, Brosnan CF, Lee SC (2004) Regulation of RANTES/CCL5 expression in human astrocytes by interleukin-1 and interferon-beta. J Neurochem 90 297-308... 

Yamashita reported anti-inflammatory effect of astaxanthin when administered with aspirin. An oral preparation has been developed by Alejung and Wadstroem for the treatment of Helicobacter infections of the mammalian gastrointestinal tract. Strong evidence suggested that astaxanthin modulated the humoral and non-humoral immune systems. It enhanced the release of interleukin-1 and tumor necrosis factor-... 

A number of diflFerent animal models of uveitis have been developed) including that induced by organ-specific ocular antigens such as retinal S-antigen, rhodopsin and lens protein (Wacker et al., 1977 Rao et al., 1979). Other models are based on the injection of proteins foreign to the host, such as intravitreal injections of albumin or 7-globulin (Zimmerman and Silverstein, 1959 Kaplan etal., 1979). More recently, a third group of models has been developed based on the injection of inflammatory mediators such as interleukins-1 and 2, and tumour necrosis factor (Bhattacherjee and Henderson, 1987 ... 

Brown, G.M., Li, X.Y. and Donaldson, K. (1991a). Secretion of interleukin 1 and tumour necrosis fector by alveolar macrophages following exposure to particulate and fibrous dusts. In Mechanisms in Fibre Carcint nesis (eds. R.C. Brown, J.A. Hoskins and N.F. Johnson) pp. 499-504. Plenum, New York. 

B21. Bertini, R., Bianchi, M., and Ghezzi, P Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J. Exp. Med 167,1708-1712 (1988). 

C5, Cannon, J. G Tompkins, R. G., and Gelfland, J. A., Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J. Infect. Dis. 161, 79-84 (1990). 

P13. Pober, J. S., Bevilacqua, M. P., Mendrick, D. L., Lapierre, L. A., Fiers, W., and Gimbrone, M., Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J. Immunol. 137,1893-1896 (1986). 

Moreb JS, Turner C, Sreerama L, ZuCALI JR, SlADEK NE, SCHWEDER M. Interleukin-1 and tumor necrosis factor alpha induce class 1 aldehyde dehydrogenase mRNA and protein in bone marrow cells. Leuk Lymphoma 1995 20 77-84. 

Ferrante, A., Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors, Immunol Ser., 57, 417, 1992. 

Suzuki, N. et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 416, 750, 2002. 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

Koenders MI, Rolls JR, Oppers-Walgreen B, van den Bersselaar L, Joosten LA, Schurr JR, Schwarzenberger P, van den Berg WB, Lubberts E Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis. Arthritis Rheum 2005 52 3239-3247. 

Barrera, P., Joosten, L. A., den Broeder, A. A., van de Putte, L. B., van Riel, P. L., and van den Berg, W. B. (2001) Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 60, 660-669. 

The increased levels of catecholamines and glucocorticoids, the increased sympathetic activity and the decreased level of insulin increase the activity of hormone-sensitive lipase in adipose tissue that is responsible for the increased rate of lipolysis. Also important are the proinflammatory cytokines, TNFa, interleukins 1 and 6. The significance of fat as a fuel in trauma explains why the cytokines have a... 

Figure 18.5 A summary of the biochemical, physiological and immunological changes brought about by cytokines in response to trauma. Cytokines can be produced in trauma from macrophages, lymphocytes, endothelial cells in the tissue that is damaged, and also by Kupffer cells if the liver is damaged. IL-1, IL-6 - interleukins 1 and 6 TNF - tumour necrosis factor, IFN - interferon.

The proinflammatory cytokines (interleukins 1 and 6 and tumour necrosis factor alpha) from macrophages are raised in depression. This leads to increased PGE2 synthesis and release which may lead to a reduction in central monoamine release. 

Greist JH, Jenike MA, Robinson DS, et al Efficacy of fluvoxamine in obsessive-compulsive disorder results of a multicentre, double-bhnd, placebo-controlled trial. European Journal of Clinical Research 7 195-204, 1995c Griffin WST, Stanley LC, Ling C, et al Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 86 7611-7615, 1989... 

Another controversial but exciting area of research is the potential role of serotonin in sleep. 5-Hydroxytryptamine may trigger slow-wave sleep (non-REM sleep), whereas the muscarinic AChR and NE are involved in REM sleep (rapid-eye-movement sleep, paradoxical sleep, dream sleep). In addition to the aminergic regulation of sleep, recent research has identified several other presumed sleep factors delta-sleep-inducing peptide, sleep-promoting substance, interleukin-1, and muramyl peptides. 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

Through regulation of gene transcription, cyclosporine inhibits interleukin-1 and interleukin-2 receptor production and secondarily inhibits macrophage-T-cell interaction and T-cell responsiveness (see Chapter 55). T-cell-dependent -cell function is also affected. 

Very recently, in 1999, an European patent was published involving the description of a pharmaceutical composition, which includes terpenoid dilactones isolated from a new strain of Oidiodendrum griseum filamentous fungi, together with some semi-synthetic derivatives from the isolated natural podolactones [7]. This pharmaceutical composition was reported to be useful for the treatment of IL-1 (interleukin-1) and TNF (tumor necrosis factor)-mediated diseases. 

Bavelloni, A. Santi, S. Sirri, A. Riccio, M. Faenza, L Zini, N. Cecchi, S. Ferri, A. Auron, P. Maraldi, N.M. Marmiroli, S. Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells. J. Cell Sci., 112, 631-640 (1999)... 

Dinarello CA. 1984. Interleukin-1 and the pathogenesis of acute phase response. NEJM. 311 1413-1418. 

Dong J, Mrabet O, Moze E, Li K, Neveu PJ. 2002. Lateralization and catecholaminergic neuroimmimomodulation prazosin, an alpha 1 / alpha 2 — adrenergic receptor antagonist, suppresses interleukin-1 and increases interleukin-10 production induced by lipopolysaccharides. Neuroimmunomodulation 10 163-168. 

Moldofsky H, Lue FA, Eisen J, Keystone E, Gorczynski RM. The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med 1986 48 309-318. 

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