Reactions to Treatment: Endotoxins, cytokines, porphyria, etc.

Bacterial Endotoxini reactions, Cytokinei (immunei) reactions and inflammationi<

These are often casually referred to as “herx” reactions, or scientifically as “herxheimer-like” alluding to the Jarisch-Herxheimer reaction to bacterial toxins specifically from syphilis. All gram-negative bacteria, of which Cpni is one, have contain Lipopolysaccharidei endotoxin which is released as a matter of course during infection and is partially responsible for the on-going symptoms of the infection. When these bacterial are killed en masse they release larger amounts of endotoxin causing significant symptoms during initial phases of treatment. If the amount of endotoxin exceeds the body's ability to get rid of it, these toxic effects can be life threatening. Even in less threatening amounts, the endotoxinsi and the resulting reactions can cause oxidative stress and damage to body organs.

Wheldon believes the immediate reactions, characterized by shivering, influenzal symptoms and general malaise, are indicative of the endotoxin itself. Dorlands Medical Dictionary adds that the condition is a short term immunological reaction which causes fever, chills, muscle pain, headaches, and skin lesions.

Cytokine reaction (immune response)-

The endotoxin stimulates a powerful cytokine reaction by the immune system, which activates macrophages and brings with it inflammation. Next the compliment cascade, and release of histamine and more inflammation. Next the coagulation cascade and more inflammation, along with lowered blood pressure. It is likely that widespread muscle, joint and connective tissue pain, dis-coordination, deep fatigue, brain fog, bowel and other organ distress, nausea, are an indication of the endotoxin-cytokine cascade when abxi treatment is initiated.

"LPSi is an incredibly potent initiator of immune cascades...you really don't need much to cause a lot of harm... We know that once the endotoxin signaling process has begun, the damage done by endotoxin is actually damage done by the immune system. Cytokinesi released in high concentrations produce overwhelming amounts of ROSi and RNS, leading to free radical production and catastrophic tissue damage. Equally overwhelming amounts of antioxidantsi are required in sustained concentrations to both prevent and combat this..." http://www.acnem.org/journal/24-1_april_2005/endotoxin.htm#15

Cpn induced secondary porphyriai<

Treatment of Chlamydia infection may exacerbate pre-existing genetic porphyria or cause a secondary acute porphyria by making the intracellularChlamydia more active or by killing infected cells that already are loaded with high porphyrin levels. Some of what is confused as a “herx” reaction to treatment is actually an acute porphyria, rather than a reaction to bacterial endotoxin which is what a herxheimer reaction is referring to.

Hemei is a Fe2+ complex. A number of critical cellular functions rely on it and the biosynthesis of heme occurs in all human cells. Toxic compounds called porphyrinogens are formed in a phase of the heme biosynthesis pathway but are quickly transformed into heme normally.

The porphyrias are consequences of any impairment of the formation of porphyrinogens or in their transformation to heme. Chlamydia interfere with this step. Porphyrins then accumulate in the cell itself, and then extracellular milieu. Within the mitochondrial matrix, the final steps in the biosynthesis of heme are halted. Depletion of host cell energy by the intracellular infection with Chlamydia species causes additional energy-related complications.

Highly simplified, heme synthesis should look like this:

Heme precursors >> porphrinogens>> transformation to heme >> increased cellular transport including ATP production.

Instead, Cpn interferes with this normal process, and this happens:

Heme precursors >> porphrinogens >> interference with transformation to heme >> build up of unstable heme precursors and porphyrins inside and outside cells >> free radical damage and reduced ATP (energy) synthesis.

Symptoms of Porphyria:

Porphyria affects either the nervous system or the skin. When porphyria affects the nervous system, it can cause chest pain, abdominal pain, muscle cramps, weakness, hallucinations, seizures, purple-red-colored urine, or mental disorders like depression, anxiety, and paranoia. When porphyria affects the skin, blisters, itching, swelling, and sensitivity to the sun can result.

Stratton's protocol suggests testing for porphyrins prior to treatment, and initiating nutritional and other interventions prior to starting treatment for Cpn to help prevent or limit secondary porphyria.

"Systemic/chronic chlamydial infectionsi have been noted to have an associated secondary porphyria. Porphyrins, including water-soluble porphyrins (e.g., delta-aminolevulinic acid and porphyrobilinogen) and fat-soluble porphyrins (e.g., coproporphyrin III and protoporphyrin) may produce clinical episodes of porphyria. The presence of such porphyrins in an individual patient with chronic/systemic chlamydial infection can be confirmed pre- and during therapy by appropriate porphyrin tests such as obtaining 24-hour urine and 24-hour stool specimens for porphyrins." (from Stratton & Mitchell's THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY: SEVENTH VERSION

Sensitivity to abxi or Flagyl

Of course, different persons can be sensitive to certain antibiotics, have allergic reactions, or adverse effects from long-term use. This must be carefully monitored by your doctor when initiating treatment and may influence the choice of agents used. Most of the antichlamydial abx's used appear to be well tolerated for long term use.

One of the reasons that the bactericidal agent used, Flagyl (metronidazolei), is pulsed for 5 days every three to four weeks in Wheldon's protocol is that it's side effects can be difficult for many people-- nausea, fatigue, toxic-feeling-- and it's longer term use increases risk of other problems. Some patients tolerate tinidazole better, a related agent, although Stratton appears to find metronidazole somewhat more potent against the cryptic non-replicating intercellulari form of Cpn.

Relapses and Pseudo-relapses In Treating Cpn in Multiple Sclerosis (MS)

(Comment from David Wheldoni's site http://www.davidwheldon.co.uk/relapse_pseudo.html<)

The relapse in early relapsing-remitting MS has a typical pathology irrespective of its location. The first visible event is the orderly, local, mass death of oligodendrocyctes, the cells which support myelini. The myelin associated with these cells then degenerates. Degenerating myelin activates an inflammatory process. When this is over, young oligodendrocytes mature and make new myelin. The clinical counterpart to this pathology (unless it occurs in a silent area) is a loss of function which worsens over several hours to two days. The loss of function remains in place until the inflammation is over and remyelinationi begins. It will thus be seen that the relapse has a definite pattern and timescale.

Some people experience strange new sensations on beginning antibiotics and are often afraid that these are relapses. While relapses can occur during the first few months of antibiotics, probably initiated by virus infections, these sensations do not fulfil the timescale criteria of true relapses and tend to change their form within a week. Sometimes, in fact, they herald a return of function. What causes these 'pseudo-relapses' I do not know, but I suspect it is rebudding of neurones which make trial-and-error connections. Synaesthesia (crossover of the senses) can sometimes result; as an example, the seeing of flashes of light when hearing a loud noise. They can be quite troubling even when improvement is taking place. Repair takes place at a cellular level; function has to be re-learned at a much higher level.