Asthma diagnosis and treatment
Chronic caregiver stress and IgE expression, allergen-induced proliferation, and cytokine profiles in a birth cohort predisposed to atopy

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Background

Psychologic stress modifies immune function and cytokine production.

Objective

We examined relationships between caregiver stress on the following markers of early childhood immune response: (1) IgE expression (n = 215); (2) mitogen-induced and allergen-specific (Dermatophagoides farinae [Der f 1] and cockroach [Bla g 2]) proliferative response (n = 114); and (3) subsequent cytokine expression (INF-γ, TNF-α, IL-10, and IL-13) in a prospective birth cohort predisposed to atopy.

Methods

Caregiver stress was measured at 2-month intervals for the first 2 years of life and yearly thereafter by using the Perceived Stress Scale. A subsequent blood sample obtained from the children (median age, 2.1 years; range, 18-32 months) was analyzed for total serum IgE level and allergen-induced proliferation quantified as the stimulation index (SI; mean thymidine incorporation of the stimulated sample divided by that of the unstimulated sample). The relationship between stress and the proliferative response (SI >3 vs SI ≤3), and total IgE level (≤100 IU/mL vs >100 IU/mL) was examined by using logistic regression. The relationship between cytokine levels and stress was analyzed by using linear regression.

Results

In adjusted analyses higher caregiver stress in the first 6 months after birth was associated with a Der f 1 SI of greater than 3 (odds ratio [OR], 1.5; 95% CI, 1.0-2.3) and nominally associated with a Bla g 2 SI of greater than 3 (OR, 1.13; 95% CI, 0.7-1.8). Higher stress between ages 6 and 18 months was associated with a high total IgE level (OR, 2.03; 95% CI, 1.1-3.6). Higher stress was significantly associated with increased production of TNF-α, with a suggested trend between higher stress and reduced INF-γ production.

Conclusion

Increased stress in early childhood was associated with an atopic immune profile in these children predisposed to atopy-asthma.

Section snippets

Methods

Participants in the Home Allergen and Asthma Study include infants and their 499 families with a history of asthma or allergy recruited within 48 hours of delivery between September 1994 and July 1996, as previously reported.19 The Brigham and Women's Hospital Human Studies Committee approved the study, and written parental informed consent was obtained.

At the home visit, when the index child was 2 to 3 months old, data were collected on environmental exposures, including dust samples analyzed

Results

Table 1 shows the distribution of sociodemographic factors, maternal asthma, and whether the child had a cold within a week of the blood draw relative to total IgE levels and allergen-specific SIs. Fig 1 contains estimates of the stress curves for the families stratified by IgE level (IgE > 100 IU/mL vs IgE ≤ 100 IU/mL) or Der f 1 SI (SI > 3 vs SI ≤ 3). In these data IgE level (mean ± SD, 40.2 ± 95.2 IU/mL; range, 2-1247 IU/mL) and Der f 1 SI (5.5 ± 6.2; range, 0.4-34.0) showed considerable

Discussion

These data demonstrate that higher early-life chronic caregiver stress was associated with increased total IgE expression and an enhanced allergen-specific proliferative response at age 2 to 3 years. Moreover, higher-level stress was associated with increased TNF-α levels by stimulated PBMCs and reduced IFN-γ levels. Exposure to stress in early development might result in functional changes in immune reactivity in susceptible children, potentiating the inflammatory response.

Serial measurement

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    During preparation of the manuscript, Dr Wright was the recipient of the Edward and Amalie Kass Fellowship at the Harvard Medical School and a Mentored Clinical Scientist Development Award from the National Heart, Lung, and Blood Institute, K08 HL04187. These analyses were also supported by the Fetzer Institute and NIH R01 #AI/EHS35786.

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