Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep. 278 28

We tested whether NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, can prevent interleukin 2 (IL-2)-induced capillary leakage in tumour-bearing mice without compromising the therapeutic benefits of IL-2. C3H/HeJ female mice transplanted s.c. with 2.5 x 10(5) C3-L5 mammary carcinoma cells were treated with: nothing, IL-2 (ten injections of 15,000 Cetus units i.p. every 8 h), L-NAME (0.1, 0.5, or 1 mg ml-1 drinking water), IL-2 + L-NAME (0.1 or 0.5 or 1 mg ml-1 drinking water). Therapies were given in one round (IL-2, days 10-13; L-NAME, days 9-13) or in two rounds (IL-2, days 10-13 and 20-23; L-NAME, days 9-13 and days 19-23) after tumour transplantation. Capillary leakage was measured from the water contents of the pleural cavities, lungs, spleen and kidneys. Effects of the therapies on the primary tumour size and the number of spontaneous lung metastases were also recorded. NO production was measured as the nitrite + nitrate levels in the serum and in the pleural effusion. After the first round of therapies, addition of L-NAME significantly reduced IL-2-induced pulmonary oedema and water retention in the spleen in a dose-dependent manner. It also significantly reduced the IL-2-induced rise in NO levels in the serum and pleural fluid, but did not affect IL-2-induced pleural effusion or water retention in the kidney. At later stages of tumour growth (day 23), tumours themselves induced significant fluid retention in the lungs and the kidney, which was not aggravated further with the second round of IL-2 therapy. At this time, L-NAME therapy alone ameliorated tumour-induced pulmonary oedema. During both rounds of therapy different doses of L-NAME alone caused a reduction of primary tumour growth as well as spontaneous lung metastases, which improved further with the addition of IL-2. The combination therapy was at least as effective as IL-2 therapy. In summary, L-NAME had anti-tumour effects in vivo, reduced the severity of IL-2-induced capillary leakage in some organs and did not compromise anti-tumour efficacy of IL-2 therapy. Thus, L-NAME could be a valuable adjunct to IL-2-based cancer therapy.
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PMID:NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, ameliorates interleukin 2-induced capillary leakage and reduces tumour growth in adenocarcinoma-bearing mice. 854 5

Nonhuman primates are the established model for evaluating toxic responses to staphylococcal enterotoxins (SEs), as they react similarly to humans. Rodents are generally considered unresponsive to SEs. Binding affinities and T-cell reactivity suggest that SE binds more efficiently to primate major histocompatability complex class II receptors than to mouse receptors. We investigated the potentiation of staphylococcal enterotoxin B (SEB) inhalation toxicity by lipopolysaccharide (LPS) in BALB/c mice. Lethality occurred only when SEB was potentiated by LPS. Neither SEB nor LPS produced lethal effects alone. Temporal responses of interleukin 1 alpha, tumor necrosis factor alpha, interleukin 2, and interferon-gamma evoked by inhaled SEB were enhanced by LPS. By 24 hr after intoxication, serum cytokines decreased to baseline levels, and consistent pulmonary perivascular leukocytic infiltrates were evident histologically. Histologic lesions induced by inhalation exposure to SEB by mice, with or without potentiation by LPS, were similar to those in the rhesus monkey. Predominant pulmonary lesions included severe, diffuse interstitial and alveolar pulmonary edema, leukocytic infiltrates, mild perivascular edema, and alveolar fibrin deposition. Although the mechanism of aerosolized SEB-induced toxicity has not been completely resolved, similarities in histologic lesions, cytokine responses, and acute dose-response suggest the LPS-potentiated mouse model may be a credible alternative to the nonhuman primate model.
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PMID:Potentiation of inhaled staphylococcal enterotoxin B-induced toxicity by lipopolysaccharide in mice. 892 84