Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome.
BACKGROUND
L-Arginine (L-Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the L-Arg-induced natural killer (NK) cell activation remains unresolved,and the effect of L-Arg on NK cells in chronic fatigue syndrome (CFS) patients has not been estimated.


METHODS
NK cell function was evaluated in 20 subjects with CFS and compared with that in 21 healthy individuals.


RESULTS
In healthy control subjects, NK activity was significantly increased after treatment with L-Arg, an NK function enhancer, for 24 h, whereas the same treatment failed to enhance NK activity in the CFS patients. We thus focused on L-Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The L-Arg-mediated NK cell activation was abolished by addition of NG-monomethyl-L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillamine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients.


CONCLUSIONS
These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients.
Ogawa
M
M
Osaka University Medical School, Osaka, Japan.
Nishiura
T
T
Yoshimura
M
M
Horikawa
Y
Y
Yoshida
H
H
Okajima
Y
Y
Matsumura
I
I
Ishikawa
J
J
Nakao
H
H
Tomiyama
Y
Y
Kanayama
Y
Y
Kanakura
Y
Y
Matsuzawa
Y
Y
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015673:Fatigue Syndrome, Chronic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000276:immunology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D017931:DNA Primers; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine