Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of a single i.v. injection of recombinant human interleukin 1 alpha (IL-1 alpha) on the morphology and the cellularity of several lymphoid organs in normal mice. The injection of 100 U of IL-1 alpha resulted in maximal neutrophilia and leukocytosis at 1 h. By 72 h, the numbers of mononuclears, but not that of polymorphonuclears, returned to baseline levels. Absolute increase in mononuclears was paralleled by relative lymphopenia. Changes in the peripheral blood coincided with rapid decrease in the spleen cellularity and white pulp volume (especially the marginal zone), and an increase in the red pulp volume. Bone marrow cellularity was increased at 1 h, but returned to control levels by 6 h after IL-1 injection. Thymus cell depletion and cortex atrophy were maximal at 6 h and could be observed throughout the experiment. These findings indicate that leukocytosis induced by a single i.v. injection of IL-1 alpha in normal mice is concomitant with a rapid cell depletion of the spleen and thymus. Morphological and cellular changes in lymphoid organs may represent the mobilization of immunocompetent cells during the development of the inflammatory response.
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PMID:Cellular and morphological changes in lymphoid organs after a single injection of interleukin 1 alpha in the mouse. 208 44

Treatment with human recombinant tumour necrosis factor-alpha (rTNF alpha) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1.0 microgram per mouse) was similar to that previously reported for the monokine rIL-1 alpha, although somewhat greater amounts of rTNF alpha than rIL-1 alpha were required. Combined administration of suboptimal concentrations of rTNF alpha and rIL-1 alpha resulted in significant enhancement of resistance beyond that obtained with either monokine alone, whereas further increases in anti-listeria resistance were not observed at doses of rTNF alpha or IL-1 alpha that were themselves capable of inducing substantial protection. Combined administration of rTNF alpha and rIL-1 alpha was associated with a delay in onset and lessening in severity of the lymphopenia that accompanied L. monocytogenes infection. The reduced bacterial burden in the spleens and livers of mice treated with rTNF alpha and rIL-1 alpha was associated with a more rapid decline in serum colony-stimulating activity. Peritoneal macrophages from rTNF alpha- and rIL-1 alpha-treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNF alpha and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration.
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PMID:Human rTNF alpha augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1 alpha. 230 86

Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes. 331 83