Effect of L-N6-(1-iminoethyl)-lysine, an inducible nitric oxide synthase inhibitor, on murine immune response induced by Actinobacillus actinomycetemcomitans lipopolysaccharide.
OBJECTIVE
Inducible nitric oxide synthase (iNOS) activity is known to regulate the immune response. The present study was carried out to determine the effect of L-N6-(1-iminoethyl)-lysine (L-NIL), an iNOS inhibitor, on the induction of immune response to Actinobacillus actinomycetemcomitans lipopolysaccharide in mice.


METHODS
BALB/c mice were sham-immunized (group I), immunized with A. actinomycetemcomitans lipopolysaccharide (group II) or treated with L-NIL and immunized with A. actinomycetemcomitans lipopolysaccharide (group III). All animals were then challenged with viable A. actinomycetemcomitans. The levels of serum nitric oxide (NO), specific immunoglobulin G (IgG) isotypes and both interferon-gamma and interleukin-4, as well as spleen cell-derived iNOS activity, before and after bacterial challenge, were assessed. The diameter of skin lesions was also determined. Serum and spleen cells from the above groups were adoptively transferred to the recipients that were then subsequently challenged with live bacteria.


RESULTS
Treatment with L-NIL suppressed serum NO and splenic iNOS activity, but enhanced serum-specific IgG2a antibody and interferon-gamma levels. The lesions in L-NIL-treated mice healed much more rapidly. Transfer with serum and cells from L-NIL-treated and A. actinomycetemcomitans lipopolysaccharide-immunized donors resulted in rapid healing of the lesions in the recipients.


CONCLUSIONS
It is suggested that treatment with L-NIL in mice immunized with A. actinomycetemcomitans lipopolysaccharide may shift the immune response towards a protective T helper 1-like immunity against A. actinomycetemcomitans-induced infection.
Sosroseno
W
W
Department of Oral Biology, School of Dental Science, Universiti Sains Malaysia, Kota Bharu, Malaysia. wsosroseno@yahoo.com
Musa
M
M
Ravichandran
M
M
Fikri Ibrahim
M
M
Bird
P S
PS
Seymour
G J
GJ
D000038:Abscess / Q000276:immunology; D000189:Actinobacillus Infections / Q000276:immunology*; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008070:Lipopolysaccharides; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008239:Lysine