Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with the protozoan Leishmania donovani can cause serious visceral disease or subclinical infection in humans. To better understand the pathogenesis of this dichotomy, we have investigated the host cellular immune response to cutaneous or visceral infection in a murine model. Mice infected in the skin developed no detectable visceral parasitism, whereas intravenous inoculation resulted in hepatosplenomegaly and an increasing visceral parasite burden. Spleen cells from mice with locally controlled cutaneous infection showed strong parasite-specific proliferative and gamma interferon (IFN-gamma) responses, but spleen cells from systemically infected mice were unresponsive to parasite antigens. The in situ expression of IFN-gamma, interleukin-4 (IL-4), IL-10, IL-12, and inducible nitric oxide synthase (iNOS) mRNAs was determined in the spleen, draining lymph node (LN), and cutaneous site of inoculation. There was considerably greater expression of IFN-gamma and IL-12 p40 mRNAs in the LN draining a locally controlled cutaneous infection than in the spleen following systemic infection. Similarly, there was a high level of IFN-gamma production by LN cells following subcutaneous infection but no IFN-gamma production by spleen cells following systemic infection. Splenic IL-4 expression was transiently increased early after systemic infection, but splenic IL-10 transcripts increased throughout the course of visceral infection. IL-4 and IL-10 mRNAs were also increased in the LN following cutaneous infection. iNOS mRNA was detected earlier in the LN draining a cutaneous site of infection compared to the spleen following systemic challenge. Thus, locally controlled cutaneous infection was associated with antigen-specific spleen cell responsiveness and markedly increased levels of IFN-gamma, IL-12, and iNOS mRNA in the draining LN. Progressive splenic parasitism was associated with an early IL-4 response, markedly increased IL-10 but minimal IL-12 expression, and delayed expression of iNOS.
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PMID:Regional differences in the cellular immune response to experimental cutaneous or visceral infection with Leishmania donovani. 942 34

A unique feature of Mycobacterium tuberculosis is its ability to establish latent infection in the human host, which can reactivate to cause disease years later. In the present study, the mechanisms involved in the control of latent tuberculous infection were examined using two murine experimental tuberculosis models. Analysis of the model involving infection of mice with a relatively low inoculum of the virulent Erdman strain of M. tuberculosis indicated that in vivo inhibition of reactive nitrogen intermediate (RNI) production by the nitric oxide synthase inhibitor aminoguanidine resulted in reactivation. This reactivation was evidenced by hepatosplenomegaly, a robust tissue granulomatous reaction, and increased bacillary load. IFN-gamma, TNF-alpha, and inducible nitric oxide synthase were all expressed throughout the latent phase of infection. Reactivation of latent tuberculous infection by aminoguanidine treatment was confirmed using a second murine tuberculosis model based on treatment with antimycobacterial drugs. Results obtained using this drug-based model also suggested the existence of an RNI-independent antimycobacterial mechanism(s) operative in the latent phase of infection. Together, these data suggest that both RNI-dependent and -independent mechanisms contribute to the prevention of tuberculous reactivation.
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PMID:Effects of aminoguanidine on latent murine tuberculosis. 946 39

Intracardial inoculation of BALB/c mice with Leishmania donovani amastigotes induced progressive visceral leishmaniasis (VL) with increasing splenic parasite load when followed upto 4-month postinfection period. In contrast, the liver parasite load reached maximum around 2-month postinfection period following which it started declining. The infection pattern differed somewhat from the earlier reports on mouse model of VL induced by intravenous inoculation of parasites with respect to the duration as well as magnitude of parasite burden in the organs (liver and spleen) and associated hepatosplenomegaly. Immunosuppression in mice with progressive VL was manifested in the form of impairment of proliferative response of the splenic mononuclear cells (SPMC) to in vitro stimulation with leishmanial antigen or the mitogen concanavalin A (ConA), although ConA stimulated cells were found to be capable of IL-2 and IFN-gamma synthesis. Differential expression of activating (IL-2, IFN-gamma and TNF-alpha) as well as deactivating (IL-4 and TGF-beta) cytokines was demonstrable in the spleen and liver of animals during the course of infection. Further, the synthesis of inducible nitric oxide synthase (iNOS) enzyme increased considerably in the liver as well as in the spleen of 4-month infected animal with parallel increase in the transcripts of the iNOS activating cytokines IFN-gamma and TNF-alpha. The temporal variation in the organ specific immune response could be related to the differential control of parasite burden in the liver and spleen of the infected host.
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PMID:Infection pattern and immune response in the spleen and liver of BALB/c mice intracardially infected with Leishmania donovani amastigotes. 1264 14