Yz. Almallah et al., Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition, EUR J CL IN, 30(1), 2000, pp. 58-65
Citations number
44
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background Altered natural killer (NK) and lymphokine-activated killer (LAK
) cell activities have been reported with ulcerative colitis (UC). Previous
ly, we have shown that in patients with UC, the n-3 polyunsaturated fatty a
cids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), s
pecifically inhibit natural cytotoxicity with clinical improvement in disea
se activity. The aim of this study therefore was to evaluate the possible m
echanism(s) involved in this inhibition, and in particular the alteration o
f production of interleukin 2 (IL2) and the arachidonic acid metabolite leu
kotriene B-4 (LTB4), both known to modulate NK cell activity.
Materials and methods Each patient with procto-colitis received either fish
oil extract (EPA 3.2 g, DHA 2.4 g; n = 9) or placebo (n = 9) daily for 6 m
onths. Monthly assessment included disease activity using clinical and sigm
oidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated
and NK cell cytotoxic activity in vitro was measured. Monthly serum samples
were analysed for LTB4, IL2 and soluble IL2 receptors (sIL2R).
Results The n-3 PUFAs group had significantly reduced NK cell activity, com
pared with the placebo group (P < 0.05, Mann-Whitney U-test). In the n-3 PU
FA group, incubation of PBMN cells for 72 h with recombinant interleukin 2
(rIL2) reversed the NK inhibition. In patients with active proctocolitis, s
erum levels of LTB4 correlated positively with NK cell cytotoxicity (r = 0.
873, P < 0.05, Kendall's correlation coefficient). After six months of n-3
PUFAs supplementation, serum levels of LTB4 were undetectable with concurre
nt significant reduction in NK cell cytotoxic activity. The latter was asso
ciated with significant reduction of serum IL2 and sIL2R levels (P < 0.05).
Conclusion This study has demonstrated both evidence of suppression of immu
ne reactivity and concurrent reduction in disease activity in patients with
proctocolitis receiving n-3 PUFAs supplementation. This may have important
implications for therapy in patients with UC.