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LPS enhanced antibacterial host defenses (ABHD) when given at low (75 μg) doses (16 of 19 mice survived 3× LD50 Escherichia coli vs 3 of 19 LPS-naive mice; p = 0.0001), but induced lethal inflammation at high (500 μg) doses (5 of 5 died). Differences in the cytokine profiles induced by these LPS doses may provide insight into the mechanism(s) of transition from beneficial to lethal LPS responses. The 75 μg LPS induced 5.9 ± 0.9 ng/ml serum IL-18 at 8 h, which decreased to 2.3 ± 0.4 ng/ml by 24 h, whereas 500 μg LPS induced 11.1 ± 1.6 ng/ml serum IL-18 levels at 8 h, which increased until death. Compared with 75 μg, higher but sublethal (150 μg) doses of LPS induced greater serum IL-18 levels and less effectively induced ABHD (3 of 8 survived). Reduction of serum IL-18 with neutralizing Ab improved the ABHD induced by 150 μg, but reduced that produced by 75 μg LPS, suggesting an optimal range of serum IL-18 level was essential for efficient ABHD. Increased expression of caspase-1 mRNA in response to the higher IL-18 levels induced at the 150 and 500 μg, but not at the 75 μg doses of LPS may represent a positive feedback regulatory loop leading to sustained serum IL-18 levels. We conclude that the regulation of serum IL-18 expression is critical to the outcome of innate immune responses to LPS.

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This study evaluated the neonatal outcome of infants with evidence of fetal exposure to cocaine, opiates, and cannabinoids. Subjects were from the newborn nursery of an inner-city university teaching hospital. Meconium from 141 infants admitted to the full-term nursery was analyzed for metabolites of opiates, cocaine, and cannabinoids. The population was 72% African-American; 82% had medical assistance; history of drug use was reported in the medical records in 18%; mean maternal age was 24.2 years; mean birth weight was 3,234 +/- 502 g; and neonatal abstinence syndrome was reported in 7%. Meconium analysis data showed the following: 52.5% were drug-free; cocaine was present in 31%, opiates in 18% (cocaine and/or opiates 39%), and cannabinoids in 17%. In 38 infants in whom urine toxicology was obtained for clinical indications, meconium was more sensitive than urine in detecting drug exposure (55.3% vs 31.5%). There was no significant difference between cocaine/opiate-exposed and drug-free infants in race, socioeconomic status, maternal age, birth weight, head circumference, length, and Apgar scores. Cocaine/opiate-exposed infants had greater length of stay and increased frequency of maternal sexually transmitted diseases during pregnancy, with a trend toward a higher percent with fetal distress.

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