Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis.

Background: We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits.

Methods: Peripheral blood mononuclear cells (PBMC) were isolated from children (n = 53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCCtrade mark) (n = 26) or a placebo (n = 27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared.

Results: The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P = 0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P = 0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r = -0.445, P = 0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P = 0.018) and HKSA (P = 0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P = 0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed.

Conclusion: The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.