Induction of inflammation as a possible mechanism of probiotic effect in atopic eczema-dermatitis syndrome.

BACKGROUND: The immunomodulating mechanisms of Lactobacillus GG (LGG) and other probiotics are poorly understood. OBJECTIVE: We studied in vivo the immunologic effects of probiotics in infants with atopic eczema-dermatitis syndrome (AEDS) and cow's milk allergy (CMA). METHODS: Two hundred thirty infants with AEDS and suspected CMA received, concomitant with elimination diet, either LGG, a mixture of 4 probiotic strains (MIX), or placebo for 4 weeks. All available paired pretreatment and posttreatment plasma samples (n = 132) were analyzed for concentrations of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, soluble intercellular adhesion molecule 1, soluble E-selectin, TGF-beta1, TGF-beta2, and C-reactive protein. RESULTS: In infants with IgE-associated AEDS, treatment with LGG induced higher C-reactive protein levels than in the placebo group (geometric mean, 0.83 microg/mL [95% CI, 0.56-0.81] vs 0.42 microg/mL [95% CI, 0.27-0.65]; P = .021). Concomitantly, IL-6 levels increased after treatment with LGG ( P = .023) but not with MIX or placebo. Soluble E-selectin levels were higher after probiotic than after placebo treatment in infants with IgE-mediated CMA (LGG geometric mean, 86.7 ng/mL [95% CI, 75.2-100]; MIX geometric mean, 91.6 ng/mL [95% CI, 74.8-111.9]; and placebo geometric mean, 64.9 ng/mL [95% CI, 53-79.3]; analysis of covariance, P = .035; LGG vs placebo, P = .023; MIX vs placebo, P = .020). Use of MIX induced an increase in plasma IL-10 levels ( P = .016). CONCLUSION: Probiotics induced systemically detectable low-grade inflammation, which might explain the clinical effects of probiotics in AEDS and CMA.

Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates.

OBJECTIVES: To study whether intrauterine growth restriction (IUGR) is associated with decreased sensitivity to the main fetal growth factor, insulin, and the effect of glucocorticoid therapy on insulin sensitivity in preterm infants. STUDY DESIGN: Newborn infants with a birth weight (BW) of< 1500 g were classified as appropriate for gestational age ([AGA], BW within +/- 1 SD, n = 10), or small for gestational age ([SGA], BW <-2 SD, n = 13); 5 AGA infants and 8 SGA infants received systemic steroids. An abbreviated modified minimal model test was performed, consisting of sequential blood samples for glucose and insulin assays, and intravenous infusions of 0.3 g/kg glucose and 0.02 U/kg regular human insulin. The insulin sensitivity index (S(I)) was calculated using a computer program. RESULTS: The basal insulin/glucose ratio (I/G) and S(I) did not differ between the AGA and SGA groups. Steroids did not influence the I/G nor the S(I) of AGA infants (10.2 +/- 6.7 vs 8.2 +/- 2.3), but decreased the S(I) in the SGA group (12.2 +/- 5.1 vs 5.3 +/- 2.7, P <.05). CONCLUSIONS: Insulin sensitivity of neonates can be measured by the modified minimal model. IUGR is not associated with impaired fetal glucose tolerance. Early neonatal steroid treatment decreases insulin sensitivity in SGA infants, which may contribute to their risk of having hyperglycemia.

Markers of inflammation in the feces of infants with cow's milk allergy.

Growing evidence exists that exposure to cow's milk elicits inflammation in the gut of infants with cow's milk allergy, irrespective of symptoms. To demonstrate inflammation and increased protein leakage from the gut during a cow's milk elimination-challenge test in fecal samples of infants presenting with different symptoms suggestive of cow's milk allergy, we measured the concentrations of alpha1-antitrypsin (AT), eosinophil cationic protein (ECP), immunoglobulin (Ig) A, and cow's milk-specific IgA antibodies, in fecal samples of 208 infants with a mean age of 7 months. Prechallenge samples were collected after a mean 3-week elimination period, and post-challenge samples were obtained 4 days after starting the challenge. Fecal levels of prechallenge total IgA (p = 0.02) and post-challenge AT (p = 0.001) were higher in infants with a positive challenge. Of these infants, pre- and post-challenge levels of ECP were higher in those reacting after 24 h than in those reacting within 1 h (p = 0.006 and p = 0.045). Prechallenge levels of ECP were higher in those showing intestinal symptoms (p = 0.008), and both pre- and post-challenge levels of total IgA were higher in those with an IgE-mediated reaction to cow's milk (p = 0.04 and p = 0.008). Regardless of the challenge result, total IgA increased during the challenge (p < 0.001 for both challenge-positive and -negative infants) and was higher in those breast-fed until the challenge than in those fed formula only (p < 0.01). Hence, in infants reacting to the cow's milk challenge, higher prechallenge levels of fecal IgA indicate increased antigenic stimuli in the gut, and higher post-challenge levels of AT reflect increased protein loss as a result of intestinal inflammation. In infants with slowly evolving gastrointestinal symptoms, increased fecal ECP may help in distinguishing patients from those who tolerate cow's milk. Individual serial follow-up of fecal IgA and ECP can be used to estimate the degree of inflammation in the gut and an appropriate time for a challenge test, but are not diagnostic tools for cow's milk allergy.

IGF-I, IGF binding protein (IGFBP)-3, phosphoisoforms of IGFBP-1, and postnatal growth in very low birth weight infants.

Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per se a major clinical challenge and may also serve as a model in studying the mechanisms of growth retardation in general. This study was undertaken to characterize the role of IGFs and their binding proteins (IGFBPs), key regulators of fetal and infant growth, during the postnatal period in VLBW infants. Forty-eight VLBW infants (gestational age 27.6 +/- 2.2 wk, birth weight 923 +/- 257 g) were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities being assessed by a rigorous protocol of repeated, frequent lower leg length and body weight measurements. All regression analyses were adjusted for postnatal age and repeated measurements. Lower leg growth velocity showed a positive correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01). Moreover, concurrent glucocorticoid dose showed a negative correlation with both IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter) insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple regression analysis, the factor remaining significantly associated with lower leg growth velocity (R(2) = 0.63) was IGF-I, and factors associated with weight growth velocity (R(2) = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio, reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant in the circulation of these infants, may thus also have properties that are at least less inhibitory, if not promoting, on the growth-stimulating action of IGF-I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in situations with a high or low insulin concentration.