Effects of N-acetylcysteine and ambroxol on the production of IL-12 and IL-10 in human alveolar macrophages.
BACKGROUND
N-acetylcysteine (NAC) and ambroxol (AMB) have recently been proposed as possible therapeutic agents in the treatment of pulmonary disorders. IL-12 plays an important role in host resistance to infection and the development of Th-1 cells. In contrast, IL-10 is involved in anti-inflammatory and immunoregulatory mechanisms.


OBJECTIVE
We investigated the effects of NAC and AMB on secretions of IL-12 and IL-10 from human alveolar macrophages.


METHODS
Alveolar macrophages were obtained from 7 healthy nonsmokers by bronchoalveolar lavage. The cells were first incubated with either NAC or AMB for 2 h and then cultured in lipopolysaccharide (LPS) solution for 24 h. IL-12 and IL-10 secretions were measured by ELISA.


RESULTS
Both NAC and AMB enhanced LPS-induced secretion of IL-12. NAC also enhanced LPS-induced IL-10 secretion, while AMB did not. The ratio IL-12/IL-10 secretion was increased by AMB, but NAC did not affect it.


CONCLUSIONS
The results suggest that NAC enhances inflammatory and immune responses and prevents excessive responses reciprocally, through keeping local balance of IL-12 and IL-10 production in alveolar macrophages at inflammatory sites of bacterial pneumonia. AMB appears to strengthen inflammatory responses and cell-mediated immunity, facilitating the development of Th-1 cells, through shifting the local balance to IL-12 dominance.
Aihara
M
M
First Department of Internal Medicine, Gunma University Faculty of Medicine, Gunma, Japan. aiharam@showa.gumma-u.ac.jp
Dobashi
K
K
Akiyama
M
M
Naruse
I
I
Nakazawa
T
T
Mori
M
M
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000551:Ambroxol / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012016:Reference Values
D005100:Expectorants; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D000551:Ambroxol; D000111:Acetylcysteine