|HUDA, M NAZMUL - University Of California
|AHMAD, SHAIKH MESHBAHU - International Centre For Diarrhoeal Disease Research
|ALAM, JAHANGIR MD - International Centre For Diarrhoeal Disease Research
|KHANAM, AFSANA - International Centre For Diarrhoeal Disease Research
|ALAM, NURE MD - International Centre For Diarrhoeal Disease Research
|RAQIB, RUBHANA - International Centre For Diarrhoeal Disease Research
Submitted to: Stress: The International Journal on Biology of Stress
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2018
Publication Date: 6/22/2018
Citation: Huda, M., Ahmad, S.D., Alam, J., Khanam, A., Alam, N., Raqib, R., Laugero, K.D., Stephensen, C.B. 2018. Infant cortisol stress-response is associated with thymic function and vaccine response. Stress: The International Journal on Biology of Stress. https://doi.org/10.1080/10253890.2018.1484445.
Interpretive Summary: Stress can have both positive and negative effects on health. Severe stress and chronic stress can negatively affect functioning of the immune system by producing high levels of the stress-hormone cortisol. At low levels cortisol can participate in activation of normal immune responses but at high levels cortisol dampens immunity, particularly by affecting the survival of T cells. T-cells develop in the thymus and are required for memory responses triggered by infections or vaccination. Animal studies and studies with isolated T cells clearly show that high cortisol levels can lead to the death of T cells in the thymus and in peripheral tissues. Measuring stress in humans often involves measuring cortisol levels in saliva or blood before and after a stressful or painful exposure. In infants, the mild pain associated with receiving an intramuscular immunization triggers an increase in cortisol. In the present study we measured a vaccine-induced cortisol response in the saliva of infants six weeks of age undergoing routine immunization in Dhaka, Bangladesh. We used this response as an index of stress, with a greater increase being indicative of a greater stress response. We examined the association of this response with various measures of immune health (e.g., size of the thymus, level of T cells in peripheral blood) and response to vaccination (e.g., vaccine-specific T-cell proliferation, skin test response and antibody response). In brief, we found that infants with a higher stress response had smaller thymuses and fewer T cells in peripheral blood. The association with thymus size was limited to boys. No significant assosiations were seen between stress and vaccine responses. These data are unique in that vaccine responses and other measures of immune function have not been previously examined in young infants. In addition, these data suggest that boy infants have a greater detrimental response to stress than do girl infants. It is not clear why boys are more susceptible to this manifestation of stress but future work will focus on whether this differential effect persists later in infancy and is associated with less effective response to vaccination.
Technical Abstract: Background: The stress response can have both positive and negative effects on immune function, though effects on the T-cell compartment can often be negative. Here we have evaluated the association of vaccination-induced cortisol responsiveness with measures of T-cell mediated immunity, including thymus size, peripheral blood levels of naïve and memory T-cells, and measures of T-cell mediated vaccine responses, including T-cell proliferation, antibody response and delayed-type hypersensitivity (DTH). Method: This study was performed among participants of a randomized, controlled trial examining the effect of vitamin A supplementation to newborn infants on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured from 229 infants (male = 107) before and 20 min after a needle stick (vaccination) at 6 weeks of age. Thymic index was determined by ultrasonography at 1, 6, 10 and 15 w of age. Naïve, memory, and vaccine-specific responses to tuberculosis (BCG), tetanus toxoid, hepatitis B virus and oral polio virus vaccination were assayed at 6 and 15 w. Results: Thymic indices at 1 (p<0.01), 6 (p<0.01), 10 (p<0.020), and 15 (p=0.012) w were negatively associated with cortisol responsiveness in male infants. Naïve helper T cells were negatively associated with cortisol responsiveness in both male and female infants at both 6 (p=0.030) and 15 (p=0.025) w of age. B lymphocytes levels in peripheral blood were positively associated (p<0.01) with cortisol responsiveness in both male and female at 15 w. DTH skin test response to BCG vaccination showed a marginal, negative association with cortisol responsiveness but the IgG response to the OPV vaccine showed a marginal positive association. Conclusion: Cortisol responsiveness during early infancy was associated with smaller thymus size in boys and fewer peripheral blood T-cells in both boys in girls, suggesting a detrimental effect of the stress response on the T-cell compartment of the immune system. Since T-cell mediated vaccine responses were not consistently associated with the stress response, the final, functional implication of cortisol responsiveness may not be detrimental.