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Pulmonary infection induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Marc B Feinstein, Dorothy A White
Purine analogues, including fludarabine, cladribine and pentostatin, modulate their effects by interrupting DNA synthesis. It has also been found that fludarabine inhibits the cytokine-induced activation of STAT1, and STAT1-dependent transcription in normal resting or activated lymphocytes. STAT1 is a molecule essential for cell-mediated immunity and the ability to control viral infections.7 These drugs are noted for the depth of immunosuppression they cause and the prolonged duration of specific effects, which can sometimes last for years. They are highly effective against lymphocytes, and their use is associated with profound lymphocytopenias. For patients taking fludarabine, for instance, there exists a marked decrease in CD4 cells. There is also an effect on B-cells, but these cells generally recover more quickly, often within a year, and the effect on immunoglobulin levels is very variable. Neutropenia can occur in some patients. Other potential immunological consequences include transient monocytopenia, transient reduction in NK cells, and variable effect on lymphocyte and NK-cell function.8 Most infections occur early in the course of treatment, even though the CD4 cell may remain very low for extended periods. This is felt to be due to improvement in monocyte function and other immune parameters CLL.8
Lead alters intracellular protein signaling and suppresses pro-inflammatory activation in TLR4 and IFNR-stimulated murine RAW 264.7 cells, in vitro
Published in Journal of Toxicology and Environmental Health, Part A, 2019
R.J. Williams, E. Karpuzoglu, H. Connell, D.J. Hurley, S.D Holladay, R.M. Gogal
Immune cell response to extracellular signals such as IFNγ, LPS or Pb, may lead to activation and nuclear accumulation of STATs resulting in cytokine or stimulant-dependent transcriptional activities (Meyer et al. 2003). Activation of STATs via phosphorylation was recognized as one of the key points in cytokine signaling pathways. STAT1 plays an important role in response to IFNγ. The activation of STAT1α (91 kDa) through the phosphorylation of Y701 (tyrosine unit) and nuclear accumulation of STAT1α (84 kDa) dimers result in activation of downstream events. STAT1β is the shorter splice variant of STAT1α; however, STAT1β dimers do not activate transcription (Baran-Marszak et al. 2004; Gao et al. 1998).