PubMed · 1931443
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J W Clark. 1991. Biological response modifiers.. https://pubmed.ncbi.nlm.nih.gov/1931443/
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Active targeting of muramyl dipeptide (MDP) to macrophages was studied by conjugation with the neoglycoprotein, mannosyl human serum albumin (mannose-HSA) using visceral leishmaniasis as the model macrophage disease. Conjugation did not decrease the affinity of the neoglycoprotein for macrophage mannose receptor. Mannose-HSA-MDP was 50 times more efficient than free MDP in inhibiting the growth of Leishmania donovani inside peritoneal macrophages. Moreover, in a 60-day murine model of visceral leishmaniasis, 95% of the spleen parasite burden was reduced by mannose-HSA-MDP at a dose of 0.5 mg/kg/day given for 4 days. Free MDP at a similar dose had very little effect. In vitro exposure of MDP caused enhanced generation of O2- by macrophages, whereas generation of nitric oxide (NO) was not induced. The elevated antileishmanial activity of MDP-treated macrophages in culture was abrogated by O2- scavengers. In contrast, considerably enhanced amounts of NO and O2- were generated from macrophages of mannose-HSA-MDP-treated animals, and their splenocytes secreted soluble factors providing all the signals required for the induction of NO biosynthesis. The increase in NO production was paralleled by a concomitant increase in antileishmanial activity, which was reversed by NO synthesis inhibitors. Splenocyte supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation by macrophages. Moreover, i.v. administration of anti-IFN-gamma and anti-TNF-alpha along with mannose-HSA-MDP greatly reduced protection against L. donovani infection. Neoglycoprotein-conjugated MDP, therefore, activated mouse macrophages in vivo to kill L. donovani, and this may depend on the physiologic generation of NO induced by IFN-gamma and TNF-alpha.
Jomol contains cell wall fragments of the bacterium Nocardia opaca composed of 40% oligopeptides, 40% lipids, 10-15% polysaccharides, and 5-10% peptidoglycans. Technetium labeled--Jomo tech--and Indium-labeled--Jomo in--preparations are used for diagnosing cancer. Jomol is promoted to cure any cancer, except Non-Hodgkin lymphoma and ovarian cancer. It is claimed that Jomol has no side effects, however chills and high fever have been observed. Following initial intensive therapy with daily injections of Jomol, a maintenance therapy is recommended to prevent relapses. One vial of Jomol or Jomo-tech costs 450.--DM. Dr. U. Ehrenfeld, an oral surgeon, developed the aqueous extract of Nocardia opaca and patented it in 1983 under the name of Jomol. Ehrenfeld is promoting Jomo-tech and Jomo-in for qualitative and semi-quantitative cancer diagnosis with whole body scintigraphy. The following action of mechanisms of Jomol are claimed: 1. Unspecific stimulation of cellular immune mechanisms, 2. xenogenization of tumor cells towards a bacterial surface by adhesion of Jomol and then attraction and activation of macrophages. Despite the positive claims of the promoters the preclinical and clinical investigations are insufficient or missing, therefore a routine treatment of malignancies with Jomol is not justified except in study protocols. Jomol is not registered at the Intercantonal Office for Drug Control in Switzerland and is not approved by the Public Health Department in Germany and is not reimbursed by most of the state health insurances.
Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.