Guest guest Posted August 23, 2005 Report Share Posted August 23, 2005 Here are some data from that paper - in a similar experiment to those in the other 2 papers which disagree 100-fold. The live vs lysed Bb may be making a big difference in these experiments. Radolf (2004 or 5) found them to differ strongly in immunogenicity, especially at certain Bb:leucocyte ratios. --------------------------------------- Cytokine and chemokine levels in whole blood cell supernatants in different patient groups following stimulation with live borrelia spirochetes. Median values (range in parenthesis) in pg/ml are given. sick more sick less asymptomatic normal, than 6 mo than 6 mo seropositve seronegative IL-10 387 (6 977) 70 (4 848) 68 (13 588) 155 (20 610) TNF-a 216 (2 2055) 36 (0 2974) 231 (2 1783) 348 (3 1502) --------------------------------------------- Pretty damn ugly data ranges there - wish they gave standard deviations or just gave all the values. > > I read the first paper, and the follow-up. These are tentative, > > first read responses: > > > > 1) It seems odd, and very frustrating, that we are told nothing > > about the duration of disease, prior treatment history, > coinfection > > test results, or current clnical presentation in these patients > > whose monocytes were assessed for cytokine release. Yet all > patients > > were from one GP's practice! How hard could it have been to > compile > > that data? > > > > Without such information, we have nothing to correlate these > > findings to but the selection criteria, which appear to have been > > that patients were making enough Bb antibodies to test positive > via > > serology. > > > > 2) There is at least one study I recall clearly that shows what at > a > > glance seems like the inverse result. Immune cells (identified as > > macrohpages, not monocytes) exposed to borrelia outer surface > > proteins in that study were seen to produce high levels of IL- 12, > > low levels of IL-10, in a ratio extreme enough to force naive T > > cells (Th0) into the Th1 phenotype. The hypothesis considered > there > > was that by generating this response, borrelial OSPs protected the > > bugs from effective antibody development, which they stated > required > > the presence of Th2 cells. > > > > 3) I suppose in a very speculative way you could reconcile the > > results by saying that the positive antibody status of the 'late > > stage' patients acrued from the higher levels of IL-10 > facilitating > > Th2 cell, antibody-forming responses vs. the inflammmatory > response > > observed in response to borrelial OSPs in the other study I am > > referring to. > > > > 4) You could end up with a forking immune response that looks a > > little like this: > > > > In response pattern 1, high levels of inflammatory cytokines are > > generated but effective antibody development is minimized. Any > bugs > > that are killed are quickly removed from the body, but not many > are. > > > > In response pattern 2, low levels of inflammatory cytokines are > > generated, but effective antibody development is increased. More > > bugs are killed, but the inflammatory process needed to get the > > lysed bugs and their toxins out of the body are indequate, > allowing > > these to accumulate. > > > > In the first response pattern, the immune system would play a > > prominent role in generating symptoms, but a minor role in > directly > > attacking the bugs. > > > > In the second response pattern, the immune system would play a > much > > reduced role in generating symptoms, a more significant role in > > attacking the bugs. The disease would actually be progressing away > > from, not toward, an 'autoimmune' model (though based on the broad > > reduction in cytokine release to ANY flavor of LPS, possibly > toward > > a model of immune deficit). > > > > One might expect the first hypothesized pattern to correspond more > > to arthralgias, the second to correspond more to central and > > peripheral nervous system disease. > > > > It's just a bunch of wild speculation on my part. What a shame > that > > we know nothing about the actual health status of those patients > > whose monocytes were studied. > > > > I would almost think it worth corresponding with the authors to > see > > if anything more can be learned. > > > > S. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted August 23, 2005 Report Share Posted August 23, 2005 If you take this report at face value, what seems most striking is that both TNF-alpha and TGF-beta (inflammatory / counter- inflammatory) are elevated in the cerebrospinal fluid of the non- chronic, suggesting a balanced immune response is needed to avoid chronicity. You're right, it interests me. Thanks for posting it. > > I read the first paper, and the follow-up. These are tentative, > > first read responses: > > > > 1) It seems odd, and very frustrating, that we are told nothing > > about the duration of disease, prior treatment history, > coinfection > > test results, or current clnical presentation in these patients > > whose monocytes were assessed for cytokine release. Yet all > patients > > were from one GP's practice! How hard could it have been to > compile > > that data? > > > > Without such information, we have nothing to correlate these > > findings to but the selection criteria, which appear to have been > > that patients were making enough Bb antibodies to test positive > via > > serology. > > > > 2) There is at least one study I recall clearly that shows what at > a > > glance seems like the inverse result. Immune cells (identified as > > macrohpages, not monocytes) exposed to borrelia outer surface > > proteins in that study were seen to produce high levels of IL- 12, > > low levels of IL-10, in a ratio extreme enough to force naive T > > cells (Th0) into the Th1 phenotype. The hypothesis considered > there > > was that by generating this response, borrelial OSPs protected the > > bugs from effective antibody development, which they stated > required > > the presence of Th2 cells. > > > > 3) I suppose in a very speculative way you could reconcile the > > results by saying that the positive antibody status of the 'late > > stage' patients acrued from the higher levels of IL-10 > facilitating > > Th2 cell, antibody-forming responses vs. the inflammmatory > response > > observed in response to borrelial OSPs in the other study I am > > referring to. > > > > 4) You could end up with a forking immune response that looks a > > little like this: > > > > In response pattern 1, high levels of inflammatory cytokines are > > generated but effective antibody development is minimized. Any > bugs > > that are killed are quickly removed from the body, but not many > are. > > > > In response pattern 2, low levels of inflammatory cytokines are > > generated, but effective antibody development is increased. More > > bugs are killed, but the inflammatory process needed to get the > > lysed bugs and their toxins out of the body are indequate, > allowing > > these to accumulate. > > > > In the first response pattern, the immune system would play a > > prominent role in generating symptoms, but a minor role in > directly > > attacking the bugs. > > > > In the second response pattern, the immune system would play a > much > > reduced role in generating symptoms, a more significant role in > > attacking the bugs. The disease would actually be progressing away > > from, not toward, an 'autoimmune' model (though based on the broad > > reduction in cytokine release to ANY flavor of LPS, possibly > toward > > a model of immune deficit). > > > > One might expect the first hypothesized pattern to correspond more > > to arthralgias, the second to correspond more to central and > > peripheral nervous system disease. > > > > It's just a bunch of wild speculation on my part. What a shame > that > > we know nothing about the actual health status of those patients > > whose monocytes were studied. > > > > I would almost think it worth corresponding with the authors to > see > > if anything more can be learned. > > > > S. Quote Link to comment Share on other sites More sharing options...
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