Plasma cytokines half-life

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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A question that arises is why plasma measurements of TNF-a and IL-1 are poor indicators of their production.

In animal models of infection or inflammation, reticuloendothelial tissue analysis reveals evidence of up-regulation of TNF-a and IL-1 gene transcription despite an inability to detect the proteins in the circulation. The reasons for the failure to detect TNF-a or IL-1 in the circulation are multiple and represent the biology of the proteins.

The production of TNF-a and IL-1 is episodic. Macrophages exposed to continuous levels of endotoxin, for example, release TNF-a and IL-1 in a single burst over several hours and then become tolerant to repeated or continued exposure. This development of tachyphylaxis (the rapid appearance of a progressive decrease in response following repetitive administration of a physiologically active substance) remains a hallmark cytokine response to exposure to bacterial cell products. Another possible reason for failing to detect TNF-a and IL-1, is that the plasma half-lives of TNF-a and IL-10 are generally less than 60 minutes, and random sampling techniques are probably too imprecise to pick up these bursts of productions More importantly, there are inhibitors and antagonists in the blood of patients, which often interfere with the immunoassays or bioassays used to quantitate TNF-a and IL-1. This becomes extremely important because the presence of these inhibitors or antagonists in the plasma may be used to document the presence of these pro-inflammatory cytokines indirectly.

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