Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

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Previously we have reported that samples of men from various populations differ in the average concentration of cholesterol in the blood serum so that, in general, the cholesterol level tends to be directly related to the proportion of the total calories provided by fats in the habitual diet of the population (1-6). Differences in the cholesterol content of these diets cannot account for the differences in the serum (7).These observations are confirmed by other recent studies (8), but the question has been asked as to whether differences in habitual physical activity could not account for the findings. The suggestion has been made that "a large muscle mass or a large energy expenditure is the effective agent and that this, not the diet, is the important element in preventing hyperlipemia" (8, p. 1010).In some areas it is easy to show that the more prosperous men, who are usually less active physically than the rest of the local population, tend to have higher cholesterol values than men representing the rest of the community. We found this to

1. Lipids exist in the blood serum as emulsions ("chylomicrons") and as solutions of lipoprotein containing proteins, cholesterol, and other lipids. Interest in relation to atherosclerosis is centered on the cholesterol and the beta lipoproteins which contain most of the cholesterol. 2. The diet influences the blood lipids in man and animals but great quantitative differences between species makes it essential to study man himself to discover the effects of the diet on the blood lipids in man. 3. The amount of lipid in the chylomicron form in the serum is practically independent of the concentration of cholesterol and lipoproteins in the serum. The correlation between the concentrations of alpha and beta lipoproteins is very low. 4. Experiments on man show that dietary cholesterol per Se, even in large amount, has no important influence on the serum cholesterol concentration but that the latter is markedly affected by the total fat content of the diet. 5. Calorie intake per se has little influence on the blood lipids. Such effect as it has may be secondary to fat metabolism differences commonly associated with differences in calorie intakes. 6. Studies on population samples of healthy men show a marked direct relationship between the content or proportion of fat in the diet on the one hand and the concentration of total cholesterol and of beta lipoproteins in the serum on the other. The effect of the diet tends to be greater in middle-aged men than in younger men. 7. The average concentration of cholesterol in the serum of men in areas where the diets are very high in fats (of the order of 40 per cent of calories), is 25 to 50 per cent greater than the average in areas where the diets are low in fats (of the order of 20 per cent, or less, of calories). 8. A significant effect of dietary fat level on the serum cholesterol concentration is evident in man in a few weeks on a changed diet. The effect tends to increase very slowly with time thereafter and it is most pronounced when comparison is made between populations habitually subsisting on different diets. 9. It is not known how the dietary fat intake exerts its controlling influence on the blood lipids of man but the mechanisms must be complex.

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