General paper on Cytokenes

[nyxie63]

www.bioscience.org/u37153137/gaDTRQo7632rgysaGWQYT64356/2004/v9/af/1460/1460.pdf

Couldn't get the .pdf to c&p. Good read in general.

[LymeEnigma]

While I was able to grasp only a portion of the text, I did find some passages interesting:

Endotoxin (LPS), administered peripherally induced greater increase in hypothalamic temperature than the cytokines used.

This would suggest (possibly?) that endotoxins are responsible for some cytokine responses...? Or that there is another mechanism involved, that takes place of the cytokine storm?

The following not only offers some explanation, but also explains why some of us find ourselves with ridiculously taxed vagus nerves:

Furthermore, it was found that injection of the IL-1β into the portal vein increases electrical activity of the vagus and that the IL-1β receptors are localized to hepatic branches of the vagus nerve (34). These findings were interpreted as meaning that LPS, by means of complement activation, increases release of cytokines from Kupffer cells, which, subsequently, activates afferent vagal fibers. This conveys the pyrogenic message to the nucleus tractus solitarius in the brain stem and via noradrenergic bundle affects the preoptic area in the hypothalamus to stimulate the local release of PGE2 (34). This appears to be a long process, however, which can hardly explain the immediate vasoconstriction and suppression of panting occuring in rabbits within seconds after LPS injection (Figure 8). It seems to be more probable, therefore, that a direct stimulation of afferent vagal fibres by LPS, rather than by cytokines, may be responsible for the „shock reaction“ preceeding the actual febrile response. Findings that injections of LPS into the subcutaneous pouch induce fever responses in absence of any cytokines in the blood or cerebrospinal fluid support this view (38). This theory does not exclude the possibility that peripheral cytokines may also activate the vagal afferents and by means of the hypothalamic PGE2 , increase temperature thresholds for induction of thermoregulatory effectors, as it typically appears during the first phase of the fever. Neither the direct effect of cytokines on hypothalamic centers can be
excluded.