National and international surveillance of communicable diseases.
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Biomedical subjects
Publications and source records attributed to K Raska.
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In the present study we have examined the effect of a Ca2+ channel blocker (verapamil) on the binding of IL-2 to its biologically active receptor (IL-2R), as well as on the release of its soluble form (sIL-2R) by peripheral blood mononuclear cells (PBMC) stimulated by a variety of stimuli. In the same culture systems, cyclosporine A (CsA) was also used as an additional dissecting tool. PHA and the Ca2+ ionophore A23187 enhanced both the percentage of PBMC binding phycoerythrin-conjugated IL-2 (PE-IL-2) and the mean fluorescence intensity of this binding. A phorbol-ester (PMA), on the other hand, enhanced only slightly the proportion of PE-IL-2 binding cells. The two stimulatory combinations (PHA/PMA and A23187/PMA) also up-regulated the proportion of PE-IL-2 binding cells and the fluorescence intensity; the PHA/PMA combination was the most potent of all stimuli used. These two stimulatory combinations, and PHA alone, were also associated with maximal in vitro release of sIL-2R. Verapamil significantly down-regulated PE-IL-2 binding in all culture systems and it convincingly inhibited the release of sIL-2R. Furthermore, this mode of action of verapamil was concentration-dependent. CsA, on the other hand, inhibited the binding of PE-IL-2 to all stimulant-activated PBMC and had only a slight inhibitory effect on the in vitro release of sIL-2R. Our results indicate that there is a correlation between the binding of IL-2 to biologically active receptors on the surface of stimulant-activated PBMC and the release of the soluble form of IL-2R by the same cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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The acute effects of hemodialysis (HD) on activation and function of mononuclear cells (MC) were studied in a model of in vitro HD. During the HD session, both cuprophan (CU) and polysulfone (PS) induced transcription of interleukin-2 receptor (IL-2R) mRNA. Expression of IL-2R on the cytoplasmic membrane, and release of soluble IL-2R (sIL-2R), however, did not change during HD, nor did responsiveness to IL-2. Polysulfone caused a slight reduction of the proliferative response to phypohemagglutinin, and of the release of sIL-2R. Hemodialysis did not induce IL-2 production, but induced IL-1 synthesis.
Interleukin-1 (IL-1) was measured in the plasma and in mononuclear cell (MC) lysates from patients on maintenance hemodialysis (HD) using either cuprophan (CU) or polysulfone (PS) membranes. Basal plasma levels of IL-1 in HD patients were significantly higher than those of uremic patients on conservative treatment or of healthy subjects. In 10 patients on conservative treatment, plasma levels of IL-1 increased significantly after 3 and 6 months of HD. During a single HD session, plasma IL-1 fell to 21% (CU) and 22% (PS) of pre-HD levels. Hemodialysis patients had a significantly higher intracellular IL-1 content than normal controls. During HD, a further increase was seen regardless of the membrane employed. A parallel in vitro study showed that IL-1 produced during HD requires at least 24 hours to be released, and that both CU and PS are able to bind and clear IL-1.
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