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Distal procto‐colitis and n ‐3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition
Author(s) -
Y Z Almallah,
A El-Tahir,
Steven Darryll Heys,
Susan Richardson,
Oleg Eremin
Publication year - 2000
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2000.00581.x
Subject(s) - polyunsaturated fatty acid , docosahexaenoic acid , eicosapentaenoic acid , natural killer cell , arachidonic acid , lymphokine activated killer cell , pharmacology , cytotoxicity , immunology , peripheral blood mononuclear cell , interleukin 2 , biology , fatty acid , medicine , endocrinology , chemistry , biochemistry , t cell , cytokine , interleukin 21 , in vitro , immune system , enzyme
Background Altered natural killer (NK) and lymphokine‐activated killer (LAK) cell activities have been reported with ulcerative colitis (UC). Previously, we have shown that in patients with UC, the n ‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), specifically inhibit natural cytotoxicity with clinical improvement in disease activity. The aim of this study therefore was to evaluate the possible mechanism(s) involved in this inhibition, and in particular the alteration of production of interleukin 2 (IL2) and the arachidonic acid metabolite leukotriene B 4 (LTB 4 ), 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 months. Monthly assessment included disease activity using clinical and sigmoidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated and NK cell cytotoxic activity in vitro was measured. Monthly serum samples were analysed for LTB 4 , IL2 and soluble IL2 receptors (sIL2R). Results The n ‐3 PUFAs group had significantly reduced NK cell activity, compared with the placebo group ( P < 0.05, Mann–Whitney U ‐test). In the n ‐3 PUFA group, incubation of PBMN cells for 72 h with recombinant interleukin 2 (rIL2) reversed the NK inhibition. In patients with active proctocolitis, serum levels of LTB 4 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 LTB 4 were undetectable with concurrent significant reduction in NK cell cytotoxic activity. The latter was associated with significant reduction of serum IL2 and sIL2R levels ( P < 0.05). Conclusion This study has demonstrated both evidence of suppression of immune 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.