Medical Hypotheses Mdcd Hypd1~8a @,~pUKLtd1992

(1992) 39,127-129

Sudden Infant Death Syndrome Immune Response

(SIDS) and the

G. M. REID 25 Gilchrist Street, Te Aroha, New Zealand

Abstract-Vitamin E pretreatment significantly prevented E. co/i-induced Disseminated Intravascular Coagulation (DIC) in rats (1). DIG, a reduction in fibrinogen and a falling platelet count and diffuse haemorrhage are part of the clinical features of Haemorrhagic Shock Encephalopathy Syndrome (HSES), recognised as a disease entity in the 1980s (2). At the SIDS Conference 1974 Reisinger described the effect of Escherichia co/i (E. co/i) endotoxin on the rabbit (3). An early effect was a reduction in fibrinogen and a falling platelet count, resulting in the release of relatively large amounts of the neuro-transmitter serotonin, stored in platelets (3, 4). Fibrinogen inhibited the release of serotonin from platelets (24). Serotonin is released from platelets during platelet aggregation (14). Platelet aggregation is inhibited by vitamin E (1). Serotonin is a neuro-transmitter associated with deep sleep, respiratory movements and cardiovascular collapse (3). Death at a later stage involved vascular permeability, edema and haemorrhage. After fibrin-platelet clots had formed DIC was present in lungs, kidneys and other organs (3). Medical researchers in Australia linked almost half of SIDS victims with a poisonous strain of intestinal E. co/i bacteria (5). Dietary selenium in the intestinal villous tip is considered a daily modulator of cytochrome P450-dependent metabolism of drugs and toxins absorbed by intestinal mucosa (6). Villous atrophy occurs in HSES (2).

Introduction

Reid (7) described two high incidence populations of SIDS. Both the geographical areas have soils deficient in selenium (Se). In New Zealand, the highest incidence of SIDS occurs in areas with low soil selenium (7, 21). In the piglet model overheating induced vitamin E deficiency in blood plasma (21). Enteric infection in the piglet enhanced zinc and selenium requirement of piglets (11). Date

received

14 February

Date

accepted

1 April

1992

It is generally accepted that SIDS peaks at about 12 weeks of age, that there is an increased incidence in boys, low birthweight infants and premature infants. Researchers at Cornell University USA found male chicks and rats differed from females in metabolism of selenium (8). They found selenium may replace vitamin E in the chick after 3 weeks of age, for an adequate immune response. Others have found that vitamin E stimulated antibody response in E. co/i infected chicks (9). Disease protection depended on strain of chick and strain and virulence of E. coli (9).

1992

127

128 The most vulnerable period for vitamin E/selenium status appears to be during the transition period between the decline of maternal antibodies and the development of the immune response. Both vitamin E and Se enhance the immune response (9, 10). Studies on the influence of enteric pathogens and necrotizing enterocolitis in the piglet demonstrated that the villi and glands of the ilium were small and few in number and the epithelium at the apex of the villus was low and columnar (11). There was decreased zinc retention, villous atrophy, thymic atrophy and a myopathy prevented by selenium supplementation, as well as other lesions in the infected piglets. Studies of small intestinal mucosal abnormalities from cases of post-perinatal death in Sheffield, described blunted villi in the small intestine, similar to the lesions in the infected piglets and in zinc deficient children in Turkey (11, 22, 23). There was an increased enteropathy among males, and it was stated that the authors did not know of any mechanism that lowers the protection of the gut, which is mediated by gender (22). Male chicks and rats differed from females in their metabolism of selenium (8) and the zinc depleted piglets with blunted villi required selenium supplementation (11). Zinc metabolism is gender related. The intestinal villous tip requires dietary selenium almost daily for optimal synthesis of heme and for cytochrome P450-dependent metabolism of ingested drugs and toxins (6). No infant with enteropathy was fully breast-fed (22). (Maternal antibodies?) Discussion Dietary Se appears to be a critical modulator of cytochrome P450-dependent metabolism of ingested drugs and toxins absorbed in the intestinal mucosa (6). The intestinal villous tip is dependent on dietary Se for optimal function. Acute dietary iron deprivation is found to be most pronounced in the villous tip, the very cells involved in absorption of ingested material. Dietary deprivation of Se, even for a single day, dramatically reduced intestinal cytochrome P450 mixed function oxidase activity. There is a gradient in cytochrome activity from crypt to tip with the height of activity along the height of the intestinal mucosal villus (6). This is to say that destruction of the cells of the intestinal villous tip, as in enteric infection and necrotizing enterocolitis, deprives the mucosal villus of its metabolic function and its absorption capacity. The impaired intestinal cytochrome P450 formation resulted from lowered ferrochelatase activity, and therefore of intestinal heme synthesis. Acute deprivation of Se for a period as short as 1 day lowered the

MEDICAL HYPOTHESES

cytochrome P450 mixed function oxidase activity by nearly 50% and ferrochelatase activity by about the same (6). Rapidly regenerating intestinal mucosal cells, in association with necrotizing enterocolitis, have an acute dependence on nutrients from exogenous sources, which in acute illness may be water of selenium deficient origin or no nutrients at all. Conclusion Arachidonate-induced respiratory distress in mice, causing sudden death, was aggravated in the Se deficient group, thought to be due to platelet aggregation (12, 13). Platelet aggregation (inhibited by vitamin E (1)) caused release of serotonin from platelets along with formation of thromboxane (14). In human studies (in vitro) it was found Se and vitamin E both inhibited platelet thromboxane release (15). People with the bacterial infection of Legionnaire’s Disease had low Se levels during the acute stage of infection but the trend was not observed in patients with pneumonia (10). Dam (16, 17, 18) identified various Se and inositol responsive nutritional diseases in his animal studies, using a high polyunsaturated fatty acid (PUFA) low vitamin E diet. High dietary inositol lessened the effect of these high PUFA diets on the incidence of exudative diathesis (cod liver oil) and encephalomalacia (linoleic acid). Dam identified intravascular coagulation in vitamin E deficient chicks. The protective effect of vitamin E pretreatment in E. cofi induced DIC in rats points to a protective mechanism for Se and inositol in similar clinical conditions in human infants. As Reislinger pointed out, serotonin release from platelets, and DIC occur at different times of the same syndrome induced by an endotoxin. In two pairs of twins HSES developed in one cotwin and the other died of SIDS. The twin pairs were 34 months of age (19). One family was recovering from chicken pox. The HSES twin patients resembled experimental DIC in rats (1) and endotoxin infused rabbits (4). Both of these experimental toxaemias resemble Reisinger’s description where early death left no symptoms and a delayed death resembled DIC. The elevated lactate found post-mortem in SIDS victims by Tiainen was said to reflect the length of the agonal period (20). The mild hyperaemia in visceral organs appears similar to Reisinger’s description of the progression in the development of DIC (3) and to Dam’s description of exudative diathesis (16). Dietary selenium absorption is a function of the

SUDDEN INFANT DEATH SYNDROME (SIDS) AND Tllh IMMUNE RESPONSE

intestinal villous tip. An effect of endotoxin-induced DIC in rats was the early reduction in fibrinogen and a falling platelet count. Vitamin E was protective. Chvapil (24) describes the inhibitory effect of zinc ions on (in vitro) platelet aggregation and serotonin release reaction. Others describe the role of arachidonic acid release from membrane phospholipids in the platelet release reaction (25). Chvapil (24) found that zinc exerted its inhibitory effect on platelets (in vitro) only in the presence of fibrinogen. Fragility of platelets increased in zinc deficiency. We have a situation where enteric infection inhibited the function of intestinal villi, and where endotoxins induced DIC and an early reduction in fibrinogen in the rat. This reduced fibrinogen level occurred at a time when zinc and fibrinogen inhibited the platelet release of scrotonin, and at a time when vitamin E was preventative in DIC and in the early reduction of fibrinogen.

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15. 16.

References 1. Yoshikawa T, Furukawa Y, Murakami M, Watanabe K, Kondo M. Effect of vitamin E on endotoxin-induced disseminated intravascular coagulation in rats. Thomb Haemostas (Stuttgart) 48: (2) 235. 1982. Dis2. Joint British Paediatric Association and Communicable ease Surveillance Centre. Surveillance scheme for haemorrhagic shock encephalopathy syndrome. Surveillance report for 1982-84. Br Med J 290: 1.578, 1985. 3. Reisinger R C. A final mechanism of cardiac and respiratory failure. p77 in SIDS 1974. Proc of the Francis E. Camps International Symposium on Sudden and Unexpected Deaths in Infancy ed Robert L. Robertson. Published by Canadian Foundation for Study of Infant Deaths. 4. Belier F K. Craeff H. Deposition of glomerular fibrin in the rabbit after infusion with endotoxin. Nature 215: 29.5, 1967. 5. Bettleheim K, Goldwater P. News Item, New Zealand Herald. November 7, 1989. 6. Pascoe A, Sakai-Wang J. Solevin E, Correia M A. Regulation of intestinal cytochrome P450 and heme by dietary nutrients. B&hem Phamracol 32: (20) 3027, 1983. Reid M. Sudden infant death syndrome. A comparison of two high incidence populations. ~142. Abstracts. Sudden Infant Death Syndrome Conference, Graz, Austria, 1988. Anon. Link found between selenium and immune response in poultry. ComeII University Agricultural and Life Sciences News, ~10, May 1983. Tengerdy R P, Mathias M M, and Nockels C F. Vitamin E.

._ I I. 18.

19.

20.

21.

22. 23.

24.

25.

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immuntty and disease resistance. p27 m Diet and Resistance to Disease. Eds Marshall Phillips and Albert Baetz. Plenum Press NY, 1981. SpaIIholz J E. Anti-inflammatory, immunological and carcinostatic attributes of selenium in experimental animals, p43 in Diet and Resistance to Disease. Eds Marshall Phillips and Albert Baetz Plenum Press, 1981. Whitenack D L. Whitehair C K, Miller E R. Influence of enteric infection on zinc utilization and clinical signs and lesions of zinc deficiency in young swine. Am J Vet Res 39: 1449. 1978. Masukawa T, Gotto J. Iwata H. Impaired metabolism of arachidonate in selenium deficient animals. Experimentia 39: 40.5. 1983. Silver M, Iloch W, Kocsis J. Ingerman C, Smith J. Arachidonic acid causes sudden death in rabbits. Science 183: 1085. 1974. Hambert M, Svensson 1. Samuelssen B. Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Nat Acad SCI 72: (8) 2994, 1975. ‘Ioivancn J J. Effects of selenmm vitamin 1 and vttamin C on human prostacyclin and thromboxane synthesis in vitro. Prostaglandins, Leukotrienes and Medicine 26: 265, 1987. Dam II, Glavind J. Alimentary exudative diathesis. Nature 3607: 1077, 1938. Dam II, Glavind J. Factors inlluencmg capillary permeability in vitamin E deficient chicks. Science 96: 235, lY42. Dam II m ‘Vitamins and Hormone Research and Applications -Interrelationships Between Vitamin E and PUFA Applications’. 20: 527, 1962. Academic Press. Trounce J Q. Lowe J. Lloyd B W. Johnson D I. Haemorrhagic shock encephalopathy and sudden infant death Iancet 337: 202, 1991. Tiainen E. Sudden infant death in southern Finland. p64. In Abstracts Sudden Infant Death Syndrome Conference. Graz. Austria, 1988. Dolamore B A, Sluis K B, McGrouther J C, Grant S. Dallow B A, Winterboum C C. Low selenium and infant heahb in Christchurch. Proc Nutr Sot NZ 15: 181. 1990. Variend S, Sutherland R. Small intestinal mucosal abnomralitics tn post-perinatal deaths. J Clin Path 37: 283, 1984. Cavdar A 0, Arcasoy A, Cin S, Babacan 1~. Goldasoglu S. Geophagia in Turkey: iron and zinc deficiency, iron and zinc absorption studies and response to zinc m geophagia studies. p71 in Zinc Deficiency in Iluman Subjects. Alan R Liss Inc NY, 1983. Chvapil M. The role of zinc on the function of some inHammatory cells. ~103 in Zinc Metabohsm: Current Aspects in He&h and Disease. Eds George J Brewer and Ananda S l’rasad. Alan R Liss Inc. NY, 1977. Schick P K. Yo B P. The role of platelet membrane phospholipids in the platelet release reaction. J Clin Invest 54: 1032, 1974.

Sudden infant death syndrome (SIDS) and the immune response.

Vitamin E pretreatment significantly prevented E. coli-induced Disseminated Intravascular Coagulation (DIC) in rats (1). DIC, a reduction in fibrinoge...
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