Mycoplasma fermentans-induced inflammatory response of astrocytes: selective modulation by aminoguanidine, thalidomide, pentoxifylline and IL-10.
Exposure of primary rat glial cells, mostly astrocytes, to heat-inactivated Mycoplasma fermentans triggers the production of tumor necrosis factor alpha (TNFalpha) nitric oxide (NO) and prostaglandin E2 (PGE2). To attenuate the production of these proinflammatory mediators, four agents: aminoguanidine, pentoxifylline, thalidomide and IL-10 were added to astrocyte cultures. Aminoguanidine (1 and 3 mM), an inhibitor of inducible nitric oxide synthase (iNOS), suppressed the production of the three mediators. TNFalpha was the most sensitive to thalidomide, showing dose-response inhibition at concentrations of 20 microg/ml, 50 microg/ml and 250 microg/ml. PGE2 was affected only by concentrations of 50 microg/ml and 250 microg/ml, whereas NO responded solely to the highest amount of this inhibitor. The cytokine IL-10, at 10 U and 50 U, inhibited only TNFalpha production. Our results imply that selective suppression of proinflammatory mediators by various agents may prove feasible for amelioration of central nervous system inflammatory diseases.
Gallily
R
R
The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Israel.
Kipper-Galperin
M
M
Brenner
T
T
D000818:Animals; D001253:Astrocytes / Q000382:microbiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology*; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use; D009175:Mycoplasma Infections / Q000188:drug therapy*; D016858:Mycoplasma fermentans; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D006146:Guanidines; D016753:Interleukin-10; D013792:Thalidomide; C004479:pimagedine; D010431:Pentoxifylline