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)

Neutrophils play an important role in the efficacy of photodynamic therapy (PDT). These leukocytes rapidly accumulate into the tumor lesion after PDT and most likely eradicate the remaining attenuated tumor cells. The underlying mechanism of the accumulation of neutrophils at the time of PDT is not known. Therefore, we determined the effect of PDT on the course of mature and immature neutrophils in the circulation of rhabdomyosarcoma-bearing rats and studied the changes in the level of interleukin (IL)-1beta as an important stimulator of the proliferation of precursor cells of the granulocyte lineage in the bone marrow. We found that the effect of PDT on tumor growth was preceded by a rapid and specific increase of the number of mature neutrophils in the peripheral blood as early as 4 h after the start of PDT treatment and reaching maximum values after 8 h. At 24 h, the neutrophil numbers in the PDT-treated rats were still elevated as compared to sham-treated rats. In sham-treated rats, the numbers of blood monocytes and lymphocytes decreased by about 50% after 2 h and returned to their normal levels as soon as 2 h later. In PDT-treated rats, the course of monocyte numbers showed a similar pattern; however, lymphocyte numbers did not reach the normal range until 24 h. The specific increment of neutrophils was preceded by an increase of band neutrophil numbers and elevated serum levels of IL-1beta which were maximal at 2 h after the start of PDT. Pearson correlation analysis showed a significant association between the serum levels of IL-1beta at this time point and the number of band neutrophils at 4 h (R2 = 0.58; P = 0.03) and the number of mature neutrophils at 8 h (R2 = 0.54; P = 0.04). This suggests that PDT evoked an IL-1-dependent increased production rate of neutrophils in the bone marrow. Further investigation showed that the injection of anti-granulocyte colony-stimulating factor (G-CSF) antibodies not only attenuated the increase in neutrophil numbers but also greatly decreased the efficacy of PDT. On this basis, we suppose that an IL-1-induced release of G-CSF by PDT underlies this nonspecific immune reaction to the tumor. Apparently, G-CSF not only stimulates the production rate of neutrophils in the bone marrow but also increases the functional activity of these leukocytes to become indispensable tumor cell killers.
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PMID:Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors. 920 52

MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes. In this study, we confirmed that Mst1-/- mice developed hypergammaglobulinemia associated with increased levels of IgG, IgA, and IgE. We also showed that uncontrolled B cell responses were resulted from the IL-4-rich environment created by CD4+ T cells. Defective MST1-FOXO1 signaling down-regulated Treg cells, resulting in the collapse of immune tolerance where the populations of Th2 and T follicular helper cells expanded. In conclusion, we suggest that MST1 acts as a molecular brake to maintain immune tolerance by regulating T cell-mediated B cell activation.
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PMID:MST1 deficiency promotes B cell responses by CD4+ T cell-derived IL-4, resulting in hypergammaglobulinemia. 2852 87