Effects of pidotimod on macrophage functions in methylprednisolone-treated mice.
CD-1 mice were treated with methylprednisolone (mPDN) 2-5 mg/kg s.c., for 11 or 6 days, in order to achieve an immunosuppressed state. For the same length of time a group of mice also received pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid. PGT/1A, CAS 121808-62-6) i.p. at 100 or 10 mg/kg. At the end of treatment, peritoneal macrophages (MO) were recovered, purified by adherence to plastic and activated in vitro with different stimuli. After 24 h of incubation, the supernatants were collected and assayed for the presence of tumor necrosis factor-alpha (TNF-alpha) and nitrite (NO2-), which is the stable derivative of nitric oxide (NO) in acqueous solution. It is well known that TNF-alpha and NO represent two out of many molecules secreted by activated MO which are essential for killing microorganisms and for natural response to infections. It was observed that MO from mPDN-treated mice were unable to produce sufficient levels of both TNF-alpha and NO when stimulated in vitro with lipopolysaccharide, IFN-gamma or conidia from an opportunistic fungus, Aspergillus fumigatus, confirming that corticosteroids are able to inhibit the antimicrobial activity of MO. However, MO from mice received mPDN plus pidotimod fully recovered the capacity to produce TNF-alpha and NO in response to the same stimuli. Optimal dose of pidotimod was 100 mg/kg. In addition, pidotimod was also able to reconstitute the cellularity of the peritoneum and of the spleens of mice immunodepressed by mPDN.(ABSTRACT TRUNCATED AT 250 WORDS)
Taramelli
D
D
Institute of Medical Microbiology, University of Milan, Italy.
Malabarba
M G
MG
Basilico
N
N
Sala
G
G
Mattina
R
R
Cocuzza
C
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000096:biosynthesis; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013172:Spores, Fungal / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D008070:Lipopolysaccharides; D013844:Thiazoles; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C064893:pidotimod; D007371:Interferon-gamma; D011761:Pyrrolidonecarboxylic Acid; D008775:Methylprednisolone