Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice made hypercholesterolemic (HC) by diet are highly susceptible to coxsackievirus (CV) B5, whereas normal adult animals remain resistant. In attempting to define those dietary-induced physiological changes which contribute to altered resistance, a strong association between accumulation of intrahepatic cholesterol and increased CV B5-induced mortality was demonstrated, with maximum susceptibility to CV coinciding with a 2.5-fold increase in the ratio of hepatic cholesterol to protein. This metabolic imbalance was associated with a lower clearance rate of CV from the blood and liver of C57BL/6 mice, although virus-specific neutralizing antibody production was unaltered. In addition to CV, HC mice were more susceptible to an intravenous inoculation of Listeria monocytogenes in comparison to controls. The macrophage stimulant Corynebacterium parvum failed to increase resistance of HC mice to a high dose of CV B4 and L. monocytogenes and failed to induce the hepatomegaly, splenomegaly, and cellular infiltrate seen in the liver and spleen of normal animals. Furthermore, the peritoneal monocytic infiltrate induced by thioglycolate in normal animals was absent in HC mice. Results from these experiments suggest that decreased resistance to CV in the HC host is attributed to a defect in the nonspecific immune responses of macrophages and monocytes which are of primary importance in resistance to this virus and other infectious agents.
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PMID:Dietary hepatic cholesterol elevation: effects on coxsackievirus B infection and inflammation. 628 92

Intraperitoneal (i.p.) exposure to propanil (3,4-dichloropropionanilide) has previously been shown to affect macrophage cytotoxicity. In this study, we compared the immunotoxic effects of propanil, after different routes of in vivo administration, on cytokine production by thioglycollate-elicited peritoneal macrophages. C57B1/6 mice were treated with either vehicle or 200 mg/kg propanil i.p., or with vehicle, 40, or 400 mg/kg propanil orally. Three or 7 days later, ex vivo production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by macrophages after lipopolysaccharide (LPS) stimulation was determined. Both oral and i.p. propanil exposure resulted in up to a 60-70% reduction in IL-6 and TNF-alpha production by the LPS-stimulated macrophages, depending on the route, postexposure time, and dose of propanil administered. Oral exposure to propanil also caused splenomegaly and thymic atrophy in animals in much the same manner as animals exposed via the i.p. route. In vitro exposure to propanil also significantly reduced macrophage cytokine production. Thioglycollate-elicited macrophages from normal mice were cultured in the continuous presence of 0, 10, or 20 microM propanil plus LPS. This exposure caused a significant reduction in IL-6 and TNF protein production by these macrophages in a concentration-dependent manner. Northern blot analysis demonstrated that the message levels of these cytokines were reduced by approximately the same percentage as the protein levels in propanil-treated macrophages, indicating a possible transcriptional or pretranscriptional target(s) for propanil.
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PMID:The immunomodulatory effects of the herbicide propanil on murine macrophage interleukin-6 and tumor necrosis factor-alpha production. 922 36

IL-33, a member of the IL-1 family, activates MAPK and NF-kappaB through its receptor ST2L and IL-1RAcP. ST2, a member of the IL-1R superfamily, is a secreted form of ST2 gene products, which has been shown to act as a decoy receptor for IL-33 and to inhibit the IL-33/ST2L/IL-1RAcP signaling pathway. In this work, we generated ST2 transgenic mice. In control mice, intraperitoneal administration of IL-33 caused an increased number of eosinophils in blood and in peritoneal cavity, an increased number of peritoneal M Phi, splenomegaly, accumulation of periodic acid-Schiff-positive material in the lung, and high concentrations of serum IL-5 and IL-13. However, these alterations were hardly detectable in ST2 Tg mice. In peritoneal M Phi from IL-33-stimulated mice, mRNA expression of M2 M Phi marker genes were increased compared with thioglycollate-elicited peritoneal M Phi. The IL-33-stimulation also increased the secretion of IL-6 from M Phi. However, when the IL-33 was preincubated with ST2 prior to its addition to the M Phi cultures, the secretion of IL-6 was attenuated. These data suggest that, though IL-33 induced the Th2-type immune responses and infiltration of M2 type M Phi into the peritoneal cavity, ST2 can downregulate these reactions both in vivo and in vitro.
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PMID:Characterization of ST2 transgenic mice with resistance to IL-33. 2066 97