Interleukin-6 , stress response

It has become clear that cytokines are potent activators of the central stress response, serving as the afferent limb of the response system during acute or chronic inflammatory stress. Several pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-a), interleukin-ip (IL-lp), and interleukin-6 (IL-6), can activate the HPA axis (Chrousos, 1995 Tsigos et al., 1997). 

Zingarelli B, Yang Z, Hake PW, Denenberg A, Wong HR (2001) Absence of endogenous interleukin 10 enhances early stress response during post-ischaemic injury in mice intestine. Gut 48 610-622... 

Inflammatory caspases (caspase-1, -4, -5,-11 and -12) constitute a subgroup of the caspase family. Caspase-1 is the best characterized member and is responsible for the proteolytic maturation and release of the pro-inflammatory cytokines pro-interleukin (IL)-1 (3 and pro-IL-18. Caspase-1 gets activated in inflammasome complexes upon cellular stress, cellular damage and infection. 

Penkowa M., Molinero A., Carrasco J., and Flidalgo J. (2001). Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures. Neuroscience 102 805-818. 

Marui et al. clarified the relation between oxidative stress in the arterial wall (in particular, the endothelium) and the development of the inflammatory response [19,25]. Expression of VCAM-1 by hmnan endothelial cells stimulated by cytokines such as interleukin-1 (IL-1) is mediated by redox-sensitive control mechanisms [25]. The redox-sensitive nature of this gene regulation was determined by the use of antioxidants that are active intracellularly. It was reported that the antioxidant pyrolidine dithiocarbamate (PDTC) inhibited the IL-1-induced endothelial expression of mRNA for VCAM-1 and was as effective as a monoclonal antibody against the VCAM-1 counterligand very late antigen-4 (VLA-4) in inhibiting binding of Molt-4 cells, which express VLA-4 [25]. 

Ideally, stress hormones damp down an immune response that has run its course. When the HPA axis is continually running at a high level, however, the damping down can have a downside, leading to decreased ability to release the interleukins and fight infection. [...] Conversely, there is evidence that a depressed HPA axis, resulting in too little corticosteroid, can lead to a hyperactive immune system and increased risk of developing autoimmune diseases - diseases in which the immune system attacks the body s own cells.19... 

As stated earlier plasma zinc concentration is low in a wide range of conditions (Halstead and Smith, 1970). One effect of stress , mediated by ACTH and cortisol, is to reduce plasma zinc. This is part of the acute phase response to accidental or surgical injury, the effect lasting for several days. Bacterial or viral infections have a similar effect. There is recent evidence that the fall in plasma zinc is part of a complex series of metabolic events induced by the humoral factors such as Interleukin 1 (Dinarello, 1982) which in turn activates interleukin-6 the active factor responsible for induction of liver... 

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