PBMCs from both atopic asthmatic and nonatopic children show a TH2 cytokine response to house dust mite allergen.

BACKGROUND: The hypothesis that in atopic diseases the T-helper response is skewed toward a T(H)2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. OBJECTIVE: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T(H)2 response and nonatopic subjects have a T(H)1 response to allergen and (2) whether atopic patients have a decreased ability to mount T(H)1 immune responses to mycobacterial antigens. METHODS: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. RESULTS: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-gamma ratio were significantly increased in subjects with atopic asthma, whereas IFN-gamma release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-gamma release, and the IL-5/IFN-gamma ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-gamma ratio in response to HDM than to PPD (a T(H)1 stimulus). CONCLUSION: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T(H)1 response to allergens, indicates that HDM stimulates a T(H)2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T(H)1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T(H)2 response.

Reduced interferon-gamma but normal IL-4 and IL-5 release by peripheral blood mononuclear cells from Xhosa children with atopic asthma.

BACKGROUND: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-gamma (IFN-gamma); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-gamma release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. OBJECTIVES: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-gamma release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. METHODS: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured. RESULTS: Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/IFN-gamma ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-alpha release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles. CONCLUSION: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-gamma release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-gamma release might be related to asthma severity.

The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome.

A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested. The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed. Forty-five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospectively. In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination. Thirty-five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development. Five infants were assessed at an earlier stage, four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment. Twenty-three (58%) of the infants were normal and 17 (42%) were abnormal, 16 with cerebral palsy and one with developmental delay. The hypoxic ischaemic encephalopathy score was highly predictive for outcome. The best correlation with outcome was the peak score; a peak score of 15 or higher had a positive predictive value of 92% and a negative predictive value of 82% for abnormal outcome, with a sensitivity and specificity of 71% and 96%, respectively. For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome.