Subject: Cytokines, Flare Cycles and the Immune System

"....It has been observed that symptoms will flare in cycles every four weeks. It is thought that this represents the organism's cell cycle, with the growth phase occurring once per month. As antibiotics will only kill bacteria during their growth phase, therapy is designed to bracket at least one whole generation cycle. This is why the minimum treatment duration should be at least four weeks. If the antibiotics are working, over time these flares will lessen in severity and duration. The very occurrence of ongoing monthly cycles indicates that living organisms are still present and that antibiotics should be continued.

... Patients on I.V. therapy who have a strong reaction at the fourth week will need to continue parenteral antibiotics for several months, for when this monthly reaction finally lessens in severity, then oral or IM medications can be substituted. Indeed, it is just this observation that guides the clinician in determining the endpoint of I.V. treatment. In general, I.V. therapy is given until there is a clear positive response, then treatment is changed to IM or po until free of signs of active infection for 4 to 8 weeks.... "

• only live Borrelia burgdorferi (Bb) would cause an inflammatory immune response (but I agree that as long as we cannot distinguish between live Bb and Bb fragments we'd better assume they are alive).
  
  
• all Bb would undergo cell division and get killed simulataneously by the cell wall antibiotics, causing a flooding of my body with proinflammatory Bb fragments (e.g. outer sphere proteins, Osp's).
  (see Remark 1).
  

• Bb or fragments of Bb reside in niches. Our immune system doesn't
  see much of them, as long as they are there.
  
  
• The niches leak: Bb (fragments) enter into compartments that are under immune system surveillance.
  
  
• The immune system responds with inflammation and elimination of the Bb (fragments).
  
  
• It does so whenever the Bb (fragment) concentration exceed some tolerance threshold.
  
  
• It stops cleaning up as soon as the Bb (fragment) level seems low enough.
  
  
• As long as the niches leak, the Bb (fragments) keep contaminating the compartments under immune surveillance and trigger a clean-up by the immune system. The reason for the ongoing immune system's oscillation between "on" and "off" is the missing memory effect, a charcteristic of the Osp's.

Remark 1 concerning kill kinetics

I think, the Bb life cycles are probably statistically distributed over time. So, during one Bb generation time the cell wall antibiotic will see half of the population undergo cell division and thus have a chance to kill this half. One needs to continue attempting to kill half the remaining population over many generation times (Example: If you want to reduce a population of 1000 Bb down to 1 Bb, you need 10 generation times. This is what the in vitro kill kinetics experiments explore.

(-) Preac-Mursic V, Marget W, Busch U, Pleterski D, Rigler S, Hagl S, Kill Kinetics of Borrelia burgdorferi, Infection, 24: 9 - 16, 1996.

(-) Agger WA, Callister SM, Jobe DA, In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone", Antimicrob Agents Chemother 1992; Aug;36(8):1788-90.


Remark 2 concerning niches

• The niches are used as "pool of unexplained phenomena" by the Burrascano group of Lyme researchers.
  
• The rest of the community seems to use the differential diagnoses (DD) as "pool of unexplained phenomena".

Jochen