This text is update of the article ''Marshall's protocol alternative explanation'' and written by sarcoidosis patient without medical education and may contain erroneous conclusions based on the citations from PubMed.

Alexander Belousov

Jan, 25, 2005

Marshall protocol from etiologic point of view

Investigators from Poland found that, the occurrence of circulating immune complexes (CIs) were higher in all the groups of patients and in resolved sarcoidosis than in the controls, while no differences among patient with stages I/II and III/IV were revealed. In sarcoidosis with stage I/II, was observed higher percentage of CIs than in the resolved sarcoidosis. The occurrence CIs in tested groups of patients is higher than in the controls.In stage I/II of sarcoidosis, occurrence of CIs was more frequent than in the resolved sarcoidosis [1].

In the former instance, by shifting the Th1/Th2 balance, an effective humoral response could develop that clears pathogenic antigens by either Fc-mediated mechanisms or from removal of relevant immune complexes through complement receptor-1–mediated pathways. In this scenario, immune complexes are not the incipient cause of granuloma formation in sarcoidosis, but rather play a role in clearing pathogenic antigens in those patients that undergo remission. The recently published finding that complement receptor-1, a glycoprotein involved with immune complex clearance from circulating erythrocytes,is a candidate susceptibility gene in sarcoidosis may be relevant to this pathway despite a lack of any association with clinical phenotype in this study. This hypothesis would be consistent with an association of circulating immune complexes with the favorable Lofgren's syndrome. In this model, the nidus for granuloma formation may be insoluble protein aggregates, possibly of microbial origins, that are initially not cleared because of an absent or ineffective humoral response within the context of a polarized and pathogenic Th1 immune response to the same antigens [2].

Th1/Th2 balance in vivo may be modulated by adoptive transfer of Th1 or Th2 cells induced in vitro. Thl cells were induced from I-Ad-binding OVA323-339-specific T-cell receptor-transgenic (TCR-Tg) mouse spleen cells by culturing with OVA323-339 peptide and antigen presenting cells (APC) in the presence of IL-2, IL-12 and anti-IL-4 mAb. Th2 cells were induced from TCR-Tg mouse spleen cells by culturing with IL-2, IL-4 and anti-IL-12 mAb in addition to OVA323-339 plus APC. Immunomodulating activities of both Th1 and Th2 cells were determined by their effect on delayed type hypersensitivity (DTH) responses or cytokine production. No significant DTH responses (footpad swelling) were observed in untreated BALB/c mice following a single injection of OVA323-339-pulsed syngeneic spleen cells. However, adoptive transfer of Th1 cells into BALB/c mice induced b dose dependent DTH responses in response to I-Ad-bound OVA323-339 but not unrelated peptide. In contrast, only slight DTH responses were detected in BALB/c mice transferred with Th2 cells. In parallel with the DTH responses, increased levels of serum IFN-gamma were demonstrated in mice adoptively transferred with Th1, while no significant increase was observed in Th2-transferred mice. In vitro analysis also demonstrated that both spleen cells and popliteal lymph node cells prepared from Th1-transferred mice showed Th1-type cytokine production, while cells obtained from Th2-transferred mice revealed Th2-dominant cytokine production. Such immune deviation induced by antigen-specific Th1 cells was demonstrated up to three months after cell transfer. Therefore, it may be possible to manipulate the Th1/Th2 balance in vivo by adoptive transfer of antigen-specific Th1 or Th2 cells [3].

These data showed, that probably for the unknown reason (for example, defect of immune system in a part of antigene presentation or intercross action of antigenes), immune system make erroneous Th1 reaction to antigene instead Th2.

Clue of Marshall’s protocol is Minocycline which produce alveolar lymphocytosis with predominantly of CD8+. As in sarcoidosis occur alveolitis with predominance CD4+ and increased CD4+/CD8+ ratio, Minocycline can decrease CD4+/CD8+, that is a target of sarcoidosis therapy. Minocycline works as superantigen and can make allergic reactions. Th2 reaction to Minocycline destroy the antigene, which cause primary erroneous Th1 reaction and resolve sarcoidosis.

Reaction to Minocycline is Th2, which destroys the antigene, which cause primary erroneous Th1 reaction. This Th2 reaction supress Th1 reaction, destroy the antigene and produce the remission of sarcoidosis. Chronic sarcoidosis - is the disability to make effective Th2 reaction, that is with defect of humoral immunity of the owner.

Because the constant inflow of antigene from an environment is unlikely, the source of causal agent of sarcoidosis is overabundant microflora growth in site of inflammation and in an intestine (microscopical funguses, eubacteria, Clostridium sp, Streptococcuses, Streptomyces and other organisms).

Also for the patients with a chronic sarcoidosis can be useful to search chronic latent infections (for example gingivitis, parodontitis, sinusitis etc) as a source of antigene and their treatment.


1. Frequency of occurrence of circulating immune complexes in sera of patients with pulmonary sarcoidosis; preliminary report Anna Dubaniewicz Department of Pathophysiology, Medical University of Gdansk, Poland

2. David R. Moller and Edward S. Chen Genetic Basis of Remitting Sarcoidosis. Triumph of the Trimolecular Complex? American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 391-395, 2002

3. Ohta A, Sato N, Yahata T, Ohmi Y, Santa K, Sato T, Tashiro H, Habu S, Nishimura T. Manipulation of Th1/Th2 balance in vivo by adoptive transfer of antigen-specific Th1 or Th2 cells. J Immunol Methods. 1997 Nov 10;209(1):85-92