Pietro Ghezzi

Interleukin 6 activity in infants and children with bacterial meningitis

Concentrations of interleukin 6 (IL-6) in cere-brospinal fluid (CSF) and serum of infants and children with bacterial meningitis were determined and correlations were sought with other indices of inflammation and with outcome. Forty-two patients ages 1 month to 15 years (mean, 2.5 years) were studied. IL-6 activity was detectable (>50 units/ml) in 30 of 36 CSF samples collected at admission from patients with meningitis and in 1 of 23 controls with fever and normal CSF findings. Mean values were 36000 units/ml (range, 151–156000). IL-6 activity in CSF persisted during the first 5 days of illness. IL-6 concentrations at admission were not associated with clinical findings, CSF leukocyte, protein and glucose concentrations, serum C-reactive protein concentration and neurologic complications or sequele.

N-Acetyl-β-d-glucosaminidase (NAG) and NAG isoenzymes in children with upper and lower urinary tract infections

The use of N-acetyl-β-d-glucosaminidase (NAG) to diagnose the site of urinary tract infection was studied in pediatric patients. Differentiation between upper and lower tract infections (UTI) was based on clinical grounds and on elevated erythrocyte sedimentation rate, C-reactive protein and fever. NAG excretion expressed as nmol · h−1 · mg− of urinary creatinine was higher in children with upper UTI (mean ± SE 906 ± 236) than in those with lower UTI (145 ± 23) or healthy children (151.6 ± 10) (p<0.01 by Duncans test). In children with upper UTI, NAG excretion fell in parallel with the remission due to antibiotic treatment. This however was not seen in children treated with aminoglycosides. A specific and significant elevation (p < 0.01) of the B isoenzyme of NAG was documented in children with upper UTI but not in those with lower UTI (B form in upper UTI 49.2% ± 3.9 versus 21.9 ± 3.3 in lower UTI; healthy children 18.9 ± 3.4). The percentage of B isoenzyme excreted was high in two children with upper UTI but was low total NAG urinary excretion, suggesting that the quantification of isoenzymes offers further specificity in diagnosis. We conclude that the measurement of NAG and its isoenzymes in children with UTI provides useful information in the diagnosis of the site of infection.

Regional Production of Nitric Oxide after a Peripheral or Central Low Dose of LPS in Mice

Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS-responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebroventricular) or systemic (intravenous) low dose of LPS (2.5 micrograms/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.