Interleukin-6 (IL-6) shares several biologic properties with IL-1, including hematopoietin-1 activity and stimulation of T cells. Because many of their biologic activities overlap, we developed and used a specific radioimmunoassay (RIA) for IL-6 to compare production of this cytokine on a molar basis with that of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF)alpha. The RIA correlated well with the hybridoma bioassay for IL-6 (r = .87, P less than .001). Freshly isolated human peripheral blood mononuclear cells (PBMC) cultured in the absence of stimuli did not produce IL-6 in most cases. Kinetics of secretion and cell-association of IL-6 were studied. In contrast to IL-1 alpha but similar to TNF, IL-6 was almost entirely secreted into the extracellular fluid. Incubation with different stimuli (lipopolysaccharide [LPS], phytohemagglutinin [PHA], Staphylococcus epidermidis, or IL-1 alpha) resulted in production of IL-6. However, on a molar basis PBMC produced approximately two to three times less IL-6 than IL-1 alpha, IL-1 beta, or TNF, regardless of the stimulus. The amount of IL-6 produced from PBMC was consistent when measured in the same subjects six time during a 12-week period. In a cohort of 38 donors, the coefficient of variation for IL-6 production was .32, compared with .92 for IL-1 beta and .96 for TNF. Comparing cytokine production by PBMC, there was a significant correlation between IL-6 and IL-1 beta (r = .72) and between IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1 beta or TNF production, but suppressed IL-1 beta and TNF production induced by LPS or PHA by 30% (P less than .01). This suppression of IL-1 beta and TNF by IL-6 appears to be on the level of transcription.

Interleukin-6 (IL-6) shares several biologic properties with IL-1, including hematopoietin-1 activity and stimulation of T cells. Because many of their biologic activities overlap, we developed and used a specific radioimmunoassay (RIA) for IL-6 to compare production of this cytokine on a molar basis with that of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF)alpha. The RIA correlated well with the hybridoma bioassay for IL-6 (r = .87, P less than .001). Freshly isolated human peripheral blood mononuclear cells (PBMC) cultured in the absence of stimuli did not produce IL-6 in most cases. Kinetics of secretion and cell-association of IL-6 were studied. In contrast to IL-1 alpha but similar to TNF, IL-6 was almost entirely secreted into the extracellular fluid. Incubation with different stimuli (lipopolysaccharide [LPS], phytohemagglutinin [PHA], Staphylococcus epidermidis, or IL-1 alpha) resulted in production of IL-6. However, on a molar basis PBMC produced approximately two to three times less IL-6 than IL-1 alpha, IL-1 beta, or TNF, regardless of the stimulus. The amount of IL-6 produced from PBMC was consistent when measured in the same subjects six time during a 12-week period. In a cohort of 38 donors, the coefficient of variation for IL-6 production was .32, compared with .92 for IL-1 beta and .96 for TNF. Comparing cytokine production by PBMC, there was a significant correlation between IL-6 and IL-1 beta (r = .72) and between IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1 beta or TNF production, but suppressed IL-1 beta and TNF production induced by LPS or PHA by 30% (P less than .01). This suppression of IL-1 beta and TNF by IL-6 appears to be on the level of transcription.

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Kiebsiella pneumoniae, a worldwide cause of nosocomial infections, is one of the most common causes of death in newborns in nurseries. In this study, we investigated the role of interleukin-1 (IL-1) in an experimental animal model of neonatal sepsis, using a natural antagonist of IL-1 receptors, the IL-1 receptor antagonist (IL-iRa), to block IL-l's effects in neonatal Kiebsiella sepsis in the absence of antibiotic treatment. Newborn Wistar-Kyoto rats were injected intraperitoneally with a single dose (10 mg/kg) of either IL-lRa (n = 43) or human serum albumin as a control (n = 40). At the same time, a 50% lethal dose ofK. pneumoniae was injected subcutaneously. No antibiotics were given at any time. After 10 days, survival was 60% for the albumin group and 80%Yo for the IL-lRa group (P < 0.01). IL-lRa treatment also afforded protection when the dose of bacteria was increased sixfold (P < 0.01). There were two episodes of leukopenia in the control group, which were suppressed by IL-lRa (P < 0.01 and P < 0.001). IL-1 and IL-6 levels were lower in the IL-lRa-treated group (P < 0.05 and P < 0.001, respectively). No differences between the two groups were observed in the number of bacteria in cultures of the blood, lungs, liver, or spleen. When IL-lRa (10 mg/kg) was given both at time zero and 24 h after bacterial challenge, lethality was significantly increased (P < 0.01). Single doses of IL-lRa of from 20 to 40 mg/kg progressively increased lethality compared with controls (P < 0.01) in both Wistar-Kyoto

In IUGR fetuses, the two segments of the PCA show signs of vasodilatation earlier than the MCA. As IUGR fetuses deteriorate, the two segments of the PCA and the MCA behave similarly.

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Abstract. Low levels of dehydroepiandrosterone (DHEA) and cortisol hormones produced by the suprarenal cortex have been associated with diseases involving chronic inflammation, low interferon (IFN)-␥, and high interleukin (IL)-6. Diffuse cutaneous leishmaniasis (DL), a long-lasting intracellular parasitic infectious disease, can spread unknown levels of DHEA and cortisol. Serum concentrations of both were measured in 5 patients with DL, in 15 patients with localized lesions produced by Leishmania (LL), and in 20 healthy volunteers. Leishmania mexicana mexicana was identified as the causal agent in patients with DL and LL. Hormone levels were lower in DL compared with controls and LL. Furthermore, we detected a lower percentage of IFN-␥-positive cells with higher levels of IL-6 and higher titers of antiLeishmania antibodies in patients with DL, whereas patients with LL were similar to controls. These data suggest that patients with DL may be good candidates for DHEA and cortisol supplementation.