Immunomodulatory and protective effects of N-acetylcysteine in mitogen-activated murine splenocytes in vitro.
N-Acetylcysteine (NAC) is a pro-glutathione drug used to treat chronic lung disorders and because of its anti-AIDS virus activity in vitro, has been proposed for AIDS therapy. The effect of NAC on mitogen-activated-lymphocyte blastogenesis in C57B1/6 mouse splenocytes and ability of NAC to protect lymphocytes against mitogen-induced cytotoxicity was examined in vitro. NAC increased splenocyte proliferation in the presence of optimal and suboptimal concentrations of concanavalin A (Con A) and lipopolysaccharide (LPS). Stimulatory and costimulatory effects of NAC on mitogen-induced responses were also evident. The dose-response relationship describing the effects of NAC on lymphocyte proliferation with Con A-induced responses were enhanced in a dose-dependent manner, whereas the corresponding LPS-induced responses increased to a maximum level followed by decline in responses at higher concentrations of NAC. When splenocytes were incubated with inhibitory supraoptimal concentrations of Con A (10 microg/ml) or LPS (150 microg/ml), NAC partially enhanced the Con A-induced response but completely prevented the inhibitory effect of supraoptimal concentrations of LPS on splenocyte blastogenesis. Optimal and supraoptimal concentrations of Con A caused activation-induced cell death in the splenocytes whereas comparable concentrations of LPS did not produce a similar effect. Splenocyte cell death produced by the optimal mitogenic concentrations of Con A was completely blocked by the addition of NAC to cultures. Immunomodulation and protective effects of NAC were observed in mitogen-activated lymphocytes in vitro.
Omara
F O
FO
Département des Sciences Biologiques et TOXEN, Université du Québec à Montréal, Canada.
Blakley
B R
BR
Bernier
J
J
Fournier
M
M
D000111:Acetylcysteine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D000276:Adjuvants, Immunologic; D008934:Mitogens; D000111:Acetylcysteine