Lipid-laden macrophages, which are predominantly derived from blood monocytes, are present at sites of active multiple sclerosis demyelination and are assumed to be involved in the demyelinating process. These inflammatory cells produce a variety of toxic oxygen metabolites which can mediate host tissue destruction. We measured production of two oxygen metabolites by monocytes and polymorphonuclear leukocytes in MS patients and controls. Stimulated monocytes produced significantly more hydrogen peroxide, superoxide, and chemiluminescence in the MS group than controls. The polymorphonuclear leukocyte, an inflammatory cell that appears to contribute little to MS demyelination, did not demonstrate increased production of toxic oxygen metabolites in the MS patients as compared to controls. These results suggest that blood monocytes in MS patients are primed to produce increased amounts of cytotoxic oxygen metabolites when exposed to inflammatory stimuli.

We found a small but statistically significant reduction in the linoleic acid concentration of white blood cells and platelets in MS patients. The percent linoleic acid concentration (mean +/- S.D.) in the white blood cells if 24 MS patients was 8.8 +/- 1.8% as compared with 11.4 +/- 4.9 in 24 age and sex-matched controls (p less than 0.05). Platelet levels were 8.5 +/- 2.4% and 10.6 +/- 3.8% respectively (P less than 0.05). Serum linoleic acid levels were not significantly different in the two groups. The possible role of linoleic acid in the pathogenesis of MS has yet to be defined.

Polymorphonuclear leukocytes (PMNLs) are an important contributor to inflammation and are thus a part of the pathophysiology of many human diseases. We assessed the effect of fish oil on PMNL inflammatory potential by measuring chemiluminescence and superoxide production before and after six weeks of daily cod liver oil ingestion by healthy volunteers. Phagocytosing PMNLs demonstrated a 27% decrease in chemiluminescence (P less than 0.05) and a 64% decrease in superoxide production (P less than 0.01), following the cod liver oil supplementation. Analysis of PMNL and platelet fatty acids revealed the appearance of eicosapentaenoic acid and a significant decrease in arachidonic acid in both types of cells.

Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.

Antiplatelet drugs as exemplified by aspirin are used frequently to prevent stroke. Aspirin inhibits the formation of both the potent platelet aggregator, thromboxane A2 and the potent anti-aggregator, prostacyclin. Another approach to the inhibition of platelet aggregation might involve selective suppression of thromboxane formation. We report our experience in swine with UK-38,485, a drug which selectively inhibits thromboxane formation. The rationale and potential uses of UK-38,485 in the in vivo prevention of platelet aggregation and for the therapy of cerebrovascular disease are discussed.