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Tolerating immunology
THE LANCET
SCIENCE AND MEDICINE
Tolerating immunology
Back stays best position for sleeping babies
L
utting babies to sleep on their back has no adverse health consequences, concludes a study of almost 10 000 infants in south-west England (Pediatrics 1997; 100: 75–78). Since the early 1990s, many health departments worldwide have advised that babies should sleep supine, because the risk of sudden infant death syndrome (SIDS) is increased for babies sleeping prone (relative risk 1·9–12·7). Parents can now be reassured Back on top that the reduced risk of cot death associated with sleeping supine is not offset by a higher risk of other disorders. The study was part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a population-based cohort study to monitor environmental features that affect health and development. Researchers at the Institute of Child Health, Bristol, surveyed mothers of singletons born between June, 1991, and December, 1992, on their baby’s sleeping position and on signs and symptoms at age 4–6 weeks and at 6–8 months. 43 health outcomes— including respiratory symptoms, gastrointestinal disorders, crying, colic, and calling a doctor to home—
ast week, researchers meeting at the Immunological Tolerance Symposium, Ciba Foundation, London, UK, estimated that cures for autoimmune diseases are still a decade away. The past 5 years have seen many spectacular advances in our understanding of the immune system, but autoimmunity—the final immune frontier—is still a mystery. In the developed world, 2–5% of the population suffer from autoimmune conditions, and many organs, and indeed lives, are wasted every year because of transplant rejection. As chairman Av Mitchinson (Forchungslaboratorium, Berlin, Germany) urged, “immunologists must deliver something therapeutic for autoimmunity and tolerance soon or [they] won’t be popular”. T cells that develop immune responses to self-proteins are killed or rendered inactive by one of many distinct self-tolerance pathways, delegates heard. Activation-induced cell death occurs when interleukin-2, expressed by T cells on antigen recognition, stimulates apoptosisinducing coexpression of the Fas protein and its ligand, FasL. Anergy, or immune apathy, results when cytotoxic T-lymphocyte antigen 4 (see Lancet, July 5, p 38) recognises B7, a T-cell-surface protein upregulated during the immune response. In mice, defects in any of these proteins result in a proliferation of anti-self T cells—ie, autoimmune disease. So researchers are working on ways to block or stimulate these proteins to induce or avert immune reactions. Some animal-model tumours, for example, have been treated by stimulating B7 expression on tumour cells with interferon-␥, to encourage destruction by the body’s defence mechanisms. The “holy grail” of immunology remains the induction of host tolerance: to donor grafts, allergens, and even gene-therapy vectors. Animal studies suggest that transplantation tolerance can be induced by blocking some T-cell-surface proteins. But, “there is a crying need to study signal transduction”, says Abul Abbas, Brigham and Women’s Hospital (Boston, MA, USA), for “only when we have fully characterised the signalling intermediates will we be able to manipulate them therapeutically with rationally designed drugs”.
P
were assessed for 9777 infants initially and for 8524 of these at 6–8 months. Only two outcomes—nappy rash at 4 weeks and cradle cap at 6 months—were significantly more common in babies who slept supine than in those babies with other sleeping positions. When ALSPAC was planned it seemed likely that there would be up to 40 cases of SIDS in the study population. But “the change in sleeping position in the population of Avon was already far advanced”, say the authors, “and there were only 5 such deaths among the 14 138 infants”. This strong shift—only 3% of babies in the survey were front sleepers, 18% slept supine, and 70% slept on their sides—meant that few correlations were statistically strong. However, say the authors, “the results indicate that infants put to sleep on their back were . . . at reduced risk of respiratory and gastrointestinal conditions, [and] those put on their side were more likely to be visited at home by a doctor for a health problem”. Front sleeping was linked with a wide range of problems, mainly respiratory. Dorothy Bonn
Smoking in pregnancy linked with conduct disorder The association remained significant after control for many confounders. “We can’t yet say with certainty that smoking during pregnancy will cause your child to have conduct disorder, but it will increase his or her likelihood to develop these problems”, says lead author Lauren Wakschlag (University of Chicago, IL, USA). “We don’t yet know the mechanism behind any link. But animal-based research indicates that smoking reduces oxygenation Cost of tobacco smoke on children to the brain of the fetus, and Parental smoking—a major preventable also affects the way that cause of morbidity and mortality among neurons make connections.” American children—leads to a yearly Wakschlag believes the study medical expenditure of US$4·6 billion and shows that smoking may cause loss-of-life costs of $8·2 billion (Arch an additional and previously Pediatr Adolesc Med 1997; 151: 645–53). unrecognised multimillion dolThe authors claim that “more young lar cost to society for treating children are killed by parental smoking than youth with conduct disorder.
oys born to women who smoke more than 10 cigarettes daily in pregnancy are 4·4 times more likely to have conduct disorder than those born to non-smokers (p=0·001). So concludes a US study of 177 boys referred to university child psychiatric or child psychology clinics (Arch Gen Psychiatry 1997; 54: 670–76). In the study, boys aged 7–12 years were regularly assessed over a 6-year period using DSM-IIIR criteria.
B
by all unintentional injuries combined”. Sara Abdulla
190
Peter Moore
Vol 350 • July 19, 1997
SCIENCE AND MEDICINE
Tolerating immunology
Back stays best position for sleeping babies
L
utting babies to sleep on their back has no adverse health consequences, concludes a study of almost 10 000 infants in south-west England (Pediatrics 1997; 100: 75–78). Since the early 1990s, many health departments worldwide have advised that babies should sleep supine, because the risk of sudden infant death syndrome (SIDS) is increased for babies sleeping prone (relative risk 1·9–12·7). Parents can now be reassured Back on top that the reduced risk of cot death associated with sleeping supine is not offset by a higher risk of other disorders. The study was part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a population-based cohort study to monitor environmental features that affect health and development. Researchers at the Institute of Child Health, Bristol, surveyed mothers of singletons born between June, 1991, and December, 1992, on their baby’s sleeping position and on signs and symptoms at age 4–6 weeks and at 6–8 months. 43 health outcomes— including respiratory symptoms, gastrointestinal disorders, crying, colic, and calling a doctor to home—
ast week, researchers meeting at the Immunological Tolerance Symposium, Ciba Foundation, London, UK, estimated that cures for autoimmune diseases are still a decade away. The past 5 years have seen many spectacular advances in our understanding of the immune system, but autoimmunity—the final immune frontier—is still a mystery. In the developed world, 2–5% of the population suffer from autoimmune conditions, and many organs, and indeed lives, are wasted every year because of transplant rejection. As chairman Av Mitchinson (Forchungslaboratorium, Berlin, Germany) urged, “immunologists must deliver something therapeutic for autoimmunity and tolerance soon or [they] won’t be popular”. T cells that develop immune responses to self-proteins are killed or rendered inactive by one of many distinct self-tolerance pathways, delegates heard. Activation-induced cell death occurs when interleukin-2, expressed by T cells on antigen recognition, stimulates apoptosisinducing coexpression of the Fas protein and its ligand, FasL. Anergy, or immune apathy, results when cytotoxic T-lymphocyte antigen 4 (see Lancet, July 5, p 38) recognises B7, a T-cell-surface protein upregulated during the immune response. In mice, defects in any of these proteins result in a proliferation of anti-self T cells—ie, autoimmune disease. So researchers are working on ways to block or stimulate these proteins to induce or avert immune reactions. Some animal-model tumours, for example, have been treated by stimulating B7 expression on tumour cells with interferon-␥, to encourage destruction by the body’s defence mechanisms. The “holy grail” of immunology remains the induction of host tolerance: to donor grafts, allergens, and even gene-therapy vectors. Animal studies suggest that transplantation tolerance can be induced by blocking some T-cell-surface proteins. But, “there is a crying need to study signal transduction”, says Abul Abbas, Brigham and Women’s Hospital (Boston, MA, USA), for “only when we have fully characterised the signalling intermediates will we be able to manipulate them therapeutically with rationally designed drugs”.
P
were assessed for 9777 infants initially and for 8524 of these at 6–8 months. Only two outcomes—nappy rash at 4 weeks and cradle cap at 6 months—were significantly more common in babies who slept supine than in those babies with other sleeping positions. When ALSPAC was planned it seemed likely that there would be up to 40 cases of SIDS in the study population. But “the change in sleeping position in the population of Avon was already far advanced”, say the authors, “and there were only 5 such deaths among the 14 138 infants”. This strong shift—only 3% of babies in the survey were front sleepers, 18% slept supine, and 70% slept on their sides—meant that few correlations were statistically strong. However, say the authors, “the results indicate that infants put to sleep on their back were . . . at reduced risk of respiratory and gastrointestinal conditions, [and] those put on their side were more likely to be visited at home by a doctor for a health problem”. Front sleeping was linked with a wide range of problems, mainly respiratory. Dorothy Bonn
Smoking in pregnancy linked with conduct disorder The association remained significant after control for many confounders. “We can’t yet say with certainty that smoking during pregnancy will cause your child to have conduct disorder, but it will increase his or her likelihood to develop these problems”, says lead author Lauren Wakschlag (University of Chicago, IL, USA). “We don’t yet know the mechanism behind any link. But animal-based research indicates that smoking reduces oxygenation Cost of tobacco smoke on children to the brain of the fetus, and Parental smoking—a major preventable also affects the way that cause of morbidity and mortality among neurons make connections.” American children—leads to a yearly Wakschlag believes the study medical expenditure of US$4·6 billion and shows that smoking may cause loss-of-life costs of $8·2 billion (Arch an additional and previously Pediatr Adolesc Med 1997; 151: 645–53). unrecognised multimillion dolThe authors claim that “more young lar cost to society for treating children are killed by parental smoking than youth with conduct disorder.
oys born to women who smoke more than 10 cigarettes daily in pregnancy are 4·4 times more likely to have conduct disorder than those born to non-smokers (p=0·001). So concludes a US study of 177 boys referred to university child psychiatric or child psychology clinics (Arch Gen Psychiatry 1997; 54: 670–76). In the study, boys aged 7–12 years were regularly assessed over a 6-year period using DSM-IIIR criteria.
B
by all unintentional injuries combined”. Sara Abdulla
190
Peter Moore
Vol 350 • July 19, 1997