The modulation of tumour necrosis factor‐α, interleukin‐1α and glucose levels with GMDP and other analogues of muramyl dipeptide

Immunomodulatory agent muramyl dipeptide (MDP) and seven of its analogues were tested for ability to counteract the toxic actions of lipopolysaccharide (LPS) in experimental mouse models. Female BALB/c mice were presensitized with Corynebacterium parvum (P. acnes) and given MDP or equimolar doses of one of its analogues after 2 weeks, followed by intravenous challenge with LPS 18 h later. This treatment produced a sharp increase in blood cytokine (TNF‐oc, IL‐la) levels 4 h after LPS administration followed by a decline to control values after 6 h. Four analogues, GMDP, threonylMDP, GMDPBenz and GMDPOBut, were able to reduce the level of cytokines induced with LPS. For most of the analogues, the higher doses reduced the levels of TNF‐a but slightly increased the concomitant IL‐lα levels. GMDP was the most effective compound tested in terms of reduction of TNF‐α and IL‐lα levels, as well as for reduction of the hypoglycaemia caused by the administration of LPS.

[1]  L. Johannsen.  Biological properties of bacterial peptidoglycan , 1993, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[2]  B. Aggarwal,et al.  Increased lymphotoxin in human malarial serum, and the ability of this cytokine to increase plasma interleukin-6 and cause hypoglycaemia in mice: implications for malarial pathology. , 1992, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[3]  T. Andronova,et al.  The control of the antibody isotype response to recombinant human immunodeficiency virus gp120 antigen by adjuvants. , 1992, AIDS research and human retroviruses.

[4]  H. Besedovsky,et al.  Metabolic and neuroendocrine effects of pro-inflammatory cytokines. , 1992, European journal of clinical investigation.

[5]  N. Kelly,et al.  Interleukin-6 is a better marker of lethality than tumor necrosis factor in endotoxin treated mice. , 1992, FEMS microbiology immunology.

[6]  H. Okamura,et al.  High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor. , 1992, Journal of immunology.

[7]  H. Starnes,et al.  Sepsis-induced cascade of cytokine mRNA expression: correlation with metabolic changes. , 1992, The American journal of physiology.

[8]  O. Zak,et al.  Enhancement of the effectiveness of antimicrobial therapy by muramyl peptide immunomodulators. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  E. Makarov,et al.  Muramyl peptide‐binding sites are located inside target cells , 1991, FEBS letters.

[10]  R. Levy,et al.  Idiotype vaccination against murine B cell lymphoma. Humoral and cellular requirements for the full expression of antitumor immunity. , 1990, Journal of immunology.

[11]  V. Ivanov,et al.  Muramylpeptides augment expression of Ia-antigens on mouse macrophages. , 1990, Biomedical science.

[12]  L. Chedid,et al.  Priming Effect of Muramyl Peptides for Induction by Lipopolysaccharide of Tumor Necrosis Factor Production in Mice , 1990, Journal of leukocyte biology.

[13]  R. Al,et al.  [Immunostimulating effects of muramyl dipeptide, glucosaminyl muramyl dipeptide and their synthetic derivatives in vitro]. , 1989 .

[14]  G. Rook,et al.  Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages. , 1989, Clinical and experimental immunology.

[15]  J. Playfair,et al.  Malarial parasites induce TNF production by macrophages. , 1988, Immunology.

[16]  L. Moldawer,et al.  Circulating interleukin 1 and tumor necrosis factor during inflammation. , 1987, The American journal of physiology.

[17]  M. Kiso,et al.  Structural requirements of muramylpeptides for induction of necrosis at sites primed with Mycobacterium tuberculosis in guinea pigs , 1987, Infection and immunity.

[18]  J. Krueger,et al.  Induction of interleukin 1 by synthetic and naturally occurring muramyl peptides. , 1986, Federation proceedings.

[19]  A. Adam,et al.  Muramyl peptides: Immunomodulators, sleep factors, and vitamins , 1984, Medicinal research reviews.

[20]  E. Lederer,et al.  Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity , 1982, Infection and immunity.

[21]  S. Schwartzman,et al.  Enhancement of endotoxic shock by N-acetylmuramyl-L-alanyl-(L-seryl)-D-isoglutamine (muramyl dipeptide). , 1979, Cancer research.

[22]  C. Adlam,et al.  Lympho-reticular stimulatory properties of Corynebacterium parvum and related bacteria. , 1973, Journal of medical microbiology.

[23]  L. Chedid,et al.  Various aspects of synergism between endotoxin and MDPs. , 1990, Advances in experimental medicine and biology.

[24]  R. Falcoff,et al.  Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha. , 1990, Immunology.

[25]  N. Bovin,et al.  [Immunostimulating effects of muramyl dipeptide, glucosaminyl muramyl dipeptide and their synthetic derivatives in vitro]. , 1989, Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic].

[26]  C. Leclerc,et al.  Selective regulation of lymphokines production by MDP: A key to its immunomodulatory activity? , 1985 .

[27]  V. T. Ivanov.  [Immunoactive peptides]. , 1984, Voprosy meditsinskoi khimii.

[28]  E. Lederer,et al.  Past, present and future of the synthetic immunoadjuvant MDP and its analogs. , 1978, Biochemical pharmacology.