The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-α, interleukin (IL)-1β, IL-4 receptor α-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1β and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.

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Tumor necrosis factor (TNF) has been implicated as one of the mediators of the immunologic and metabolic changes in endotoxemia. Under adverse conditions, TNF can also be cytotoxic, and its effects can ultimately contribute to organ failure. This study shows that a 30-min infusion of a nonlethal dose of TNF induced the release of superoxide anion (0.9 nmol.min-1.g-1) by the in situ perfused rat liver. TNF also primed the liver to generate more superoxide anion (2.0 nmol.min-1.g-1) in response to an in vitro challenge with phorbol 12-myristate 13-acetate (PMA). Kupffer cells are most likely responsible for the superoxide anion production under these conditions, because the isolated Kupffer cells from TNF-infused rats produced increased quantities of superoxide anion (4-8 nmol/10(6) cells) when subsequently treated in vitro with either PMA or opsonized zymosan (control less than 1 nmol/10(6) cells). Thus, under these experimental conditions, TNF in vivo primed the Kupffer cells, but not the hepatocytes, endothelial cells, and the blood or hepatic neutrophils, to release more superoxide anion. These studies indicate that during a short-term nonlethal TNF infusion, Kupffer cells are a major target of TNF action, leading to the release of toxic-oxygen metabolites that may contribute to organ failure.