Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence suggests a link between immediate hypersensitivity and cellular immunity. In this study, we examined the effect of interleukin 2 (IL-2) on basophil histamine release. Histamine-releasing activity of IL-2 was very weak with % histamine release of 2.9 +/- 1.3 (mean +/- SEM, n = 9) at 1:12 dilution. IL-2 at 1:1200 dilution slightly inhibited anti-IgE-induced histamine release by 22.4 +/- 18.6% (P greater than 0.05). There was a significant potentiation of release at 1:12 dilution of IL-2 with % enhancement of 78.7 +/- 42.2 (P less than 0.05). IL-2 enhanced the calcium ionophore A23187-induced histamine release in a dose-dependent fashion. IL-2 at 1:12 dilution significantly potentiated release by 28.8 +/- 6.3% (P less than 0.05). There was a slight suppression of formyl-methionyl-leucyl-phenylalanine (FMLP)-induced histamine release at 1:1200 dilution with % inhibition of 23.4 +/- 7.4 (P greater than 0.05). At 1:12 dilution, IL-2 significantly potentiated FMLP-induced release by 73.7 +/- 41.6% (P less than 0.05). Recombinant IL-2 (RIL-2) augmented anti-IgE-induced histamine release with a significant enhancement at 200 units/ml. Conventional IL-2 was more potent than RIL-2 in enhancing release. These results indicate that IL-2 enhances basophil histamine release and some part of the effect of IL-2 on basophils is derived from other factors contained in conventional IL-2.
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PMID:Effect of interleukin 2 on basophil histamine release. 243 59

The systemic administration of lymphokine activated killer (LAK) cells and recombinant interleukin-2 (RIL-2) is effective in reducing the number of established pulmonary and hepatic metastases from multiple murine tumors and has recently been shown to be effective in mediating the regression of metastatic cancer in humans as well. The generation of sufficient numbers of LAK cells for the effective therapy of human tumors remains a major obstacle to the widespread application of this immunotherapeutic approach. We have thus studied methods for the in vitro expansion of LAK cells effective in immunotherapy. Our previous studies used LAK cells generated in culture with RIL-2 for 3 days. LAK cells cultured in RIL-2 for 5 or 7 days were not significantly different from cells cultured for 3 days either in the number of cells obtained, their in vivo cytotoxicity or their in vivo therapeutic effectiveness. When day 3 LAK cells were transferred to fresh culture medium containing 1000 U/ml of RIL-2, a highly reproducible expansion of these cells was obtained. By day 5, cell numbers expanded 9.6 +/- 0.8-fold (mean +/- SEM; n = 36) and by day 8, cells expanded 15.1 +/- 1.0-fold (n = 19). In 4 h 51Cr release assays against fresh tumor target cells, day 3 LAK cells had a mean of 13 lytic units/10(6) cells in 24 experiments. Day 5 expanded LAK cells had a mean of 30 lytic units/10(6) cells in 13 experiments (P less than 0.05 compared to day 3 LAK cells) and day 8 expanded LAK cells had a mean of 11 lytic units/10(6) cells in 6 experiments (P = NS compared to day 3 LAK cells) When day 5 and day 8 expanded LAK cells were infused in vivo with RIL-2, they were found to significantly reduce the number of experimentally induced pulmonary metastases as effectively as non-expanded conventional day 3 LAK cells. Similar findings were documented in experiments against hepatic metastases. These experiments demonstrate that LAK cells could expand a mean of 15-fold in vitro in RIL-2 and maintain their anti-tumor therapeutic effectiveness when adoptively transferred. These experiments suggest methods for generating increased numbers of cells for use in the adoptive immunotherapy of human cancers and may substantially reduce the need for repeated leukophereses of cancer patients undergoing this therapy.
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PMID:Optimal methods for generating expanded lymphokine activated killer cells capable of reducing established murine tumors in vivo. 287 49

The recent availability of recombinant human interleukin-2 (RIL-2) has increased interest in the potential clinical use of this lymphokine. We have examined the biologic effects of intermittent bolus and continuous intravenous administration of RIL-2 in rats. The mean (+/- SEM) half-life after an intravenous bolus injection of RIL-2 was determined to be 2.9 +/- 0.5 min (n = 4). The administration of intermittent intravenous bolus injections of RIL-2 of doses up to 10(6) units/kg every other day for 2 weeks was well tolerated without toxicity as determined by organ histology and serum chemistries. The continuous intravenous infusion of RIL-2 through an indwelling external jugular vein catheter was tolerated for 2 weeks at doses less than or equal to 3,000 U/kg/h and was associated with no abnormal serum chemistries or organ pathology. By contrast, animals that received less than 10,000 U/kg/h demonstrated RIL-2 toxicity leading to death of treated rats. Serum chemistries revealed a fourfold increase in serum glutamate oxaloacetic transaminase and serum glutamate pyruvic transaminase. Liver histology revealed hepatocellular necrosis with mononuclear cell infiltration. The thymus was depleted of lymphocytes and lymphoid infiltrates were present in liver, spleen, and lung. This is the first documentation of toxicity secondary to RIL-2 administration and suggests that hepatopathy may be the dose-limiting toxicity accompanying the administration of RIL-2.
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PMID:Toxicity of recombinant human interleukin-2 in rats following intravenous infusion. 387 93

The production of recombinant human interleukin-2 (RIL-2) in large amounts has made possible studies of the in vivo effects of this lymphokine in the normal murine host. We have studied a variety of routes of administration of RIL-2 in mice to maximize the bioavailability of this lymphokine. The serum half-life after intravenous administration was 1.6 +/- 0.3 min (mean +/- SEM, n = 3). Intraperitoneal and subcutaneous administration resulted in RIL-2 serum levels greater than or equal to 10 units/ml for 3-5 h, and was prolonged by gelatin for 7-11 h. Continuous infusion of RIL-2 was accomplished with osmotic pumps placed intraperitoneally or subcutaneously, and resulted in RIL-2 serum levels greater than or equal to 8 units/ml for greater than 4 days. RIL-2 given intraperitoneally three times daily for 3 days enhanced natural killer activity of splenocytes as measured by lysis of YAC cells. Specific augmentation of C57BL/6 splenocyte cytotoxicity to a secondary challenge of irradiated allogeneic P815 was found in mice receiving RIL-2 intraperitoneally three times daily for 3 days. The continuous administration of RIL-2 over a 4-day period resulted in the in vivo generation of lymphokine-activated killer cells in the spleen and peritoneal exudate. The exogenous administration of RIL-2 in the normal murine host enhances three different cell-mediated cytotoxic mechanisms and has potential applications in the treatment of tumors and immunodeficient conditions.
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PMID:Systemic administration of recombinant human interleukin-2 in mice. 633 41