The Answer is yes, LPS-induced time- and Dose-dependent release of some cytokines, but it is not powerful activator of some other cytokines.

Several factors you should be aware of:

1- the concentration of LPS (10-1000ng/ml)

2- Type of cells, cell line/ isolated cells (monocytes/ T cells..etc) or PBMC,

3- Time of exposure usually up to 24hrs is sufficient to yield significant amount

Martin: Temporally, its the LPS that leads to cytokines -- also termed "Pro-inflammatory Cytokines" generation. These are TNF-alpha, Interleukin-beta, and interleukin-6, as prototypes. I believe you are not referring to "anti-inflammatory cytokines". When Once LPS --> cytokines are released, they induce the so-called innate inflammatory respons, which initially is systemic. There are copious data that the latter in turn induces "Neuroinflammation".

Along these lines you might be able to read further on induction of variable inflammation scenarios in my following recent publications.

1. Daulatzai, MA. QUINTESSENTIAL RISK FACTORS: THEIR ROLE IN PROMOTING COGNITIVE DYSFUNCTION AND ALZHEIMER’S DISEASE. Neurochem Res. 2012 Dec;37(12):2627-58.

2. Daulatzai, MA. Death by a thousand cuts in Alzheimer's disease: hypoxia--the prodrome. Neurotox Res. 2013 Aug;24(2):216-43.

3. Daulatzai, MA. Neurotoxic Saboteurs: Straws that Break the Hippo's (Hippocampus) Back Drive Cognitive Impairment and Alzheimer's Disease. Neurotox Res. 2013 Oct;24(3):407-59.

I do discuss proinflammatory scenarios in some other papers, that you should be able to read, from Pubmed.

Dr. Mak Adam Daultzai

University of Melbourne, Australia

Also note the type of LPS used, with smooth LPS being the most biologically relevant and the high doses (100-1000 ng/ml) being less or not at all biologically relevant.

You may also like to consider that LPS can/often induce the release of ATP that also has effects on LPS stimulated cells to release cytokines via costimulation of P2X7 receptors or other nucleotide receptors. As a few examples see:

* Kukulski, F., F. Ben Yebdri, J. Lefebvre, M. Warny, P.A. Tessier & J. Sévigny. (2007) Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo. J. Leukoc. Biol. 81: 1269-75.

* Lévesque, S.A., F. Kukulski, K. Enjyoji, S.C. Robson & J. Sévigny. (2010) NTPDase1 governs P2X7-dependent functions in murine macrophages. Eur. J. Immunol. 40: 1473-85.

* Kukulski, F., F. Bahrami, F. Ben Yebdri, J. Lecka, M. Martín-Satué, S.A. Lévesque & J. Sévigny. (2011) NTPDase1 controls IL-8 production by human neutrophils. J. Immunol. 187: 644-53.

I am not completely sure of the premise of the question. If the cytokines you refer to in the first sentence are induced by LPS, then they can be involved (along with LPS, per se) in the induction of "tolerance" in which subsequent LPS exposure or under some circumstances exposure to a pathogen produces a less vigorous inflammatory response that can decrease resistance to infection. However, I have seen a few papers indicating increased resistance if the pathogen challenge follows the LPS closely (while cytokines are still upregulated by the LPS). The most recent "buzz" seems to be the role of M1/M2 macrophage transition and of various categories of innate lymphocytes in the mechanisms by which these phenomena occur. Sorry I don't have references handy on this, but will try to get back to this and edit to add a few later.

Dear all,

Thanks all for your replies. The focus of my question is not so much what LPS does to cytokines, but how intraindividual temporal _variability_ of cytokines secretion patterns relates to inflammatory status (i.e., even without overt cytokine increase).

Did someone study that?

To draw the analogy for you I mention the concept of the heart rate variability that is known to be highly correlated to health and disease states and literally shrinks to zero when the brain death occurs. It is in fact used as a tool to confirm brain death, at least in some jurisdictions.