Gene expression for interleukin-2 and tumor necrosis factor-alpha in the spleen of old rats under physiological condition and during septic shock. Possible pharmacological modulation.
Older individuals are more susceptible to infectious agents than younger and this is related to the disrepair of the immune defence mechanisms associated with aging. In this study we evaluated the activity of a new biological response modifier (BRM), pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in relation to the expression of some cytokine genes. We utilized 24 month-old Sprague-Dawley rats (n = 24), randomly divided into 4 groups: controls (n = 6), pidotimod-treated (n = 6; 200 mg/kg i.p., for 10 days), infected (n = 6; i.p. infection of E. coli CH 198) and pidotimod-treated + infected (n = 6). Poly(A+)RNA purified from the spleens of the animals killed 48 h after the infection was probed with Interleukin-2 (IL-2) and Tumor Necrosis Factor-alpha (TNF-alpha) cDNA clones. Northern blot analysis showed a slight signal of the IL-2 steady state mRNA in the groups of control, pidotimod-treated and infected animals, with an increase (20%) evident only in pidotimod + infected rats, 48 h after E. coli injection. On the contrary, the TNF-alpha mRNA levels were easily detectable in controls and infected rats and lower (20%, 40%) following the drug treatment, independent of i.p. infection. These results account for the BRM activity of pidotimod.
Annoni
G
G
Institute of Internal Medicine, University of Milan, Italy.
Arosio
B
B
Santambrogio
D
D
Cullurà
D
D
Gagliano
N
N
Uslenghi
C
C
D000375:Aging / Q000276:immunology; D000818:Animals; D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007155:Immunologic Factors; D007376:Interleukin-2; D013844:Thiazoles; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid