Resumo

CIANCIARULLO, Marco Antonio et al. Pro-inflammatory and anti-inflammatory mediators in neonatal sepsis: association between homeostasis and clinical outcome. Rev. bras. crescimento desenvolv. hum. [online]. 2008, vol.18, n.2, pp.135-147. ISSN 0104-1282.

OBJECTIVES: to evaluate the utility of pro-inflammatory cytokines (TNF-±, IL1-², and IL- 6) and anti-inflammatory cytokines (IL-10 and IL-1Ra) for the diagnosis of neonatal sepsis, and to verify if the homeostasis of these mediators might determine the clinical outcome. METHOD: prospective cohort study including 31 newborns with neonatal sepsis whose diagnosis was made on the basis of clinical signs and positive blood culture, or high C-reactive protein. Newborns were classified in two groups: sepsis and favorable outcome, and severe sepsis with unfavorable outcome (septic shock and/or DIVC and/or FMOS and/or death). On days 0 (diagnosis), 3 and 7 after diagnosis, serum levels of TNF-±, IL-1², IL-6, IL-10, and IL-1Ra were measured. Statistical analysis included mean values, standard deviation, median, and minimum and maximum values of all mediators, as well as the construction of mean profiles for each patient and then for both groups (with standard errors). The ANOVA with repetitive measures was used to compare cytokines variation according to time. The significance level for all statistical analyses was 5%. RESULTS: the newborns who evolved favorably presented serum levels of TNF-±, IL-1² and IL-10 very close to the minimum levels detectable by the method, whilst in the newborns with severe sepsis, these cytokine levels were significantly higher (p<0.01). IL-6 and IL-1Ra serum levels were always high irrespective of the day analyzed, and even higher in the group with unfavorable outcome (p<0.01). IL-6/IL-1Ra ratio in the group with sepsis and favorable outcome showed predominance of antiinflammatory response (r >1) on day 0, and inversion on days 3 and 7. On the contrary, IL-6/IL- 1Ra ratio was >1 on day 0 and 3, and <1 only on day 7 in the group of sepsis and unfavorable outcome. CONCLUSIONS: the analyzed mediators were effective to diagnose neonatal sepsis, and also as predictive factors of disease severity, mainly with regard to IL-6 and IL-1Ra. There was a homeostatic equilibrium represented by the IL-6/IL-1Ra in the group with sepsis and favorable outcome, in which pro-inflammatory factors were predominant on day 0 (r>1), and there was a ratio inversion on days 3 and 7 (r <1), and a homeostatic imbalance in the other group (r>1 on days 0 and 3). In the latter group the persistence of pro-inflammatory predominance versus antiinflammatory factors on day 3 after diagnosis of sepsis was correlated to clinical outcome.

Palavras-chave : Newborn; sepsis; Pro-inflammatory mediators (TNF-± , IL1-², IL-6); Anti-inflammatory mediators (Il-10, IL-1Ra); Ratio IL-6/IL-1Ra.

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