Donatella Francesca Angelone

Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-α production in vitro and in vivo

Human newborns are susceptible to microbial infection related to incompletely defined aspects of the neonatal immune system. To characterize neonatal innate immunity, we studied production of two early response cytokines in response to Toll-like receptor (TLR)-activating microbial stimuli in vitro: the pro-inflammatory cytokine tumor necrosis factor (TNF)-α and IL-6, a multifunctional cytokine with antiinflammatory and Th2-polarizing properties. Neonatal cord blood responses to multiple TLR agonists, including poly dI:dC (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), and CpG DNA (TLR9), are characterized by a higher IL-6/TNF-α ratio than in adult peripheral blood. Robust LPS-induced IL-6 production is due to both neonatal cellular (monocyte-) and humoral (serum-) factors. Remarkably, serum collected from newborns during the first week of life demonstrates higher IL-6/TNF-α ratios than does cord blood, associated with elevations of the IL-6-inducible acute phase reactants CRP and LPS-binding protein in the first days of life. A high ratio of stimulus-induced IL-6/TNF-α production is likely to profoundly modulate both innate and adaptive immune responses in the human newborn.

Role of spiramycin/cotrimoxazole association in the mother-to-child transmission of toxoplasmosis infection in pregnancy.

The purpose of this report is to evaluate the efficacy and safety of spiramycin/cotrimoxazole in the mother-to-child transmission of Toxoplasma gondii infection. We retrospectively analysed 76 infants born to mothers with toxoplasmosis during pregnancy and estimated the risk of mother-to-child transmission considering the gestational age at the time of infection. Seventy-six mothers were given spiramycin, cotrimoxazole and folinic acid; only two babies (2.6%) were infected by Toxoplasma and none of them showed signs or symptoms of congenital infection or interference of sulphamid on tetrahydrofolate reductase (THFR) either at birth or during follow-up. Treatment did not need to be stopped in any mother because of adverse drug effects. Our results seem to encourage the use of spiramycin/cotrimoxazole in women with toxoplasmosis during pregnancy.

Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome.

A 3-month-old child was first treated for incomplete Kawasaki syndrome with three cycles of intravenous immunoglobulins and aspirin, then with methylprednisolone which led to fever remission. The same child was re-hospitalized after a 10-month-period of well-being for the suspicion of a new episode of Kawasaki syndrome, which appeared to be immunoglobulin-resistant: extensive testing failed to provide an alternative diagnosis of any infectious or infiltrative disease. Diagnosis of systemic onset-juvenile idiopathic arthritis was postulated upon the long persistence of fever and inflammatory signs, which subsided only after starting corticosteroid treatment.

Kawasaki syndrome and concurrent Coxsackie virus B3 infection

We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.

Seizures in an interferon-treated child

Interferon-treated patients can present seizures, which in most paediatric cases are related to fever. The case of chronic hepatitis C is described in which Interferon probably disclosed a latent epilepsy. The hypothesis is advanced that seizures can be provoked by Interferon therapy in subjects with a low convulsant threshold and, in those cases in which it cannot be substituted with another drug, antiepileptic therapy should be started after the first episode.