Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.
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PMID:[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors]. 182 63

Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies. Toxicity was dose related and included fever, chills, malaise, arthralgias, myalgias, and unexpectedly, weight gain related to marked fluid retention. All patients receiving more than 10(5) U/kg total cumulative dose developed evidence of fluid retention, and all patients requiring discontinuance of RIL 2 (11/20) received total doses of between 2.54 X 10(5) U/kg to 15.4 X 10(5) U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 10(6) U/kg by bolus administration. IL 2 was rapidly cleared from the plasma, with a half life of 6.9 min, and a later delayed clearance was consistent with a two-compartment model, with slower release from the extravascular space back into the plasma compartment. A marked change in lymphoid cells in the periphery was noted with an early depletion of all lymphoid cells, followed by an expansion of such cells with continuous IL 2 administration. A twofold to 16-fold expansion of total lymphoid cells in the peripheral blood could be demonstrated. TAC+ cells representing up to 25% of the circulating peripheral blood mononuclear cells could be demonstrated with 3 wk of continuous RIL 2 administration. Interferon-gamma levels increased in patients treated with IL 2. Precursors of lymphokine-activated killer cells generated under standard conditions were depleted within 2 to 3 min after IL 2 administration, but repopulated the peripheral blood after 7 to 10 days of continuous IL 2 administration. No tumor regression was seen in any of the cancer patients treated with IL 2 alone.
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PMID:In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. 299 18

Forty patients with refractory malignancies were treated with recombinant human interleukin 2 (IL2) in a cooperative phase I study. IL2 was administered intravenously in six groups of patients at doses of 1 x 10(4), 3.3 - 5 x 10(4), 1 x 10(5), 3.3-5 x 10(5), 1 x 10(6) and 3.3 x 10(6) U/day and subcutaneously in 4 patients at a dose of 1 x 10(6) U/day for 5 days, respectively. Toxicity was dose related and consisted of fever and chills (52.7%), gastrointestinal disturbance (19.4%), rash, arthralgia, eosinophilia and hepatotoxicities. All the patients recovered from these soon after the administration was completed. Hypotension was observed in 3 patients at a dose of 3.3 x 10(6) U/day and in one instance was so severe that withdrawal was necessary. Enhancement in NK and LAK cell activity was noted at doses of 1 x 10(6) U/day or higher. This investigation indicates that the optimal dose is 1 x 10(6) U/day and will aid in the design of a phase 2 study with IL2.
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PMID:[A phase I study of recombinant interleukin 2 (S6820)]. 305 43

Recombinant human interleukin 2 was administered to 10 patients with chronic type B hepatitis as a part of a pilot study to evaluate its antiviral activity. Patients received 1 to 3 x 10(5) units per day of interleukin 2 for 21 to 28 days, and all completed the treatment schedule. During therapy, serum values of DNA polymerase decreased in 6 and became negative in four patients. However, when therapy was discontinued, DNA polymerase levels increased to pretreatment levels in most cases. Serum HBeAg levels did not change during treatment. Serum aminotransferase levels transiently increased in 6 of the 10 patients during therapy; but once therapy was stopped, levels fell markedly. Side effects of interleukin 2 therapy included fever, chills, anorexia and fatigue. After 1 year of follow-up, three treated patients had lost HBeAg and had marked improvement in aminotransferase levels. These serologic and biochemical improvements occurred 1.5 to 11 months after therapy was stopped. Whether a 3- to 4-week course of interleukin 2 therapy leads to an increased rate of seroconversion from HBeAg to antibody in chronic type B hepatitis deserves further evaluation in prospectively randomized, controlled trials.
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PMID:Pilot study of recombinant human interleukin 2 for chronic type B hepatitis. 313 Dec 27

A total of 12 patients with cancer or the acquired immunodeficiency syndrome have been treated with Jurkat-derived purified human interleukin 2 (IL 2). The toxicity was dose-related and consisted primarily of fever, chills, malaise, and mild reversible hepatic dysfunction. No evidence of clinical efficacy was seen when IL 2 was administered at doses of up to 2000 micrograms by bolus or continuous infusion once a week for 4 wk. No significant chronic immunologic effects (changes in mitogen responsiveness of induction of cytotoxic cells) were demonstrated. IL 2 was measured in the serum of patients, and a half-life of approximately 5 to 7 min was demonstrated with a second component of clearance of 30 to 120 min. Heating the serum at 56 degrees C for 30 min allowed for detection of smaller quantities of IL 2 by removing a serum inhibitor whose effect was seen at dilutions of up to 1/80 in our biologic assay. Sustained levels of IL 2 could be maintained by continuous infusion. Acute effects of IL 2 administration included a rapid decrease in peripheral mononuclear cells with a shift to cells of macrophage lineage and a rapid decrease in total T lymphocytes and T lymphocyte subsets. IL 2 responsiveness of peripheral mononuclear cells decreased within 15 min of IL 2 administration, with a concurrent decrease in the ability to generate lymphokine-activated killer cells. These changes did not recover until 48 hr after IL 2 administration. A rise in serum ACTH and cortisol levels was seen after the administration of 1 to 2 mg of IL 2. Future studies will evaluate the role of larger quantities of recombinant IL 2 given alone or in conjunction with in vitro-generated lymphokine-activated killer cells.
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PMID:In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2. 387 Oct 99