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)

The effect of polyinosinic-polycytidylic acid (poly I:C) treatment on the rat graft-versus-host reaction (GVHR) initiated in parental to F1 hybrid strain combinations differing at either major or minor histocompatibility determinants were studied in three different protocols. 1 A GVHR initiated in juvenile (LBN)F1 recipients and treated concurrently with poly I:C alone produced neither splenomegaly nor dermatitis in these juvenile rats. (2) Pretreatment of L donors with a single injection of poly I:C 3 days before initiation of the GVHR enhanced resultant splenomegaly in the newborn (LBN)F1 recipients. A high poly I:C dose was inhibitory. (3) Newborn recipients which received lymphocytes from L donors and which were concurrently treated with poly I:C developed dermatitis at an accelerated rate. However, poly I:C alone given to newborns mimicked the GVHR by induction of a syndrome characterized by splenomegaly, dermatitis, thymic involution, and body growth retardation. The parental L and (LF)F1 hybrid strain combination differing only at a minor histocompatibility determinant or in an isogenic hybrid combination (LBN)F1 leads to (LBN)F(1) developed no GVHR when recipients were treated with poly I:C. We conclude that poly I:C can stimulate a rat GVHR initiated with unsensitized donor cells differing at a major histocompatibility locus.
 ...
PMID:Stimulation of rat graft-versus-host reactions by polyinosinic-polycytidylic acid. 23 51

The use of inbred mouse strains of defined genetic background has allowed for the development of systems capable of reproducibly generating either an acute or chronic graft-versus-host disease (GvHD). The malononitrilamides MNA 279 and MNA 715, analogues of the main metabolite of leflunomide, have been shown to directly inhibit T-cell proliferation and B-cell functions. Therefore, they have been studied in a local GvH reaction in the popliteal lymph node (PLN) assay in LBN rats, on the development of an acute and lethal GvHD in B6C3F1 mice and on a chronic autoimmune GvHD in BDF1 hybrid mice. In the PLN assay an oral administration of various concentrations (7.5 to 50 mg/kg) of both MNAs inhibited the localized GvH reaction dose-dependently and suppressed the lymph node hyperplasia. Both MNAs also acted therapeutically in this assay when they were given as late as day 4 or 5 after challenge. In the model of an acute lethal GvHD the treatment of the GvH-B6C3F1 hybrid mice with the MNAs (2.5 to 20 mg/kg/day) shortly after disease induction on days 3 to 12 resulted in a dose-dependently improved survival rate. With 20 mg/kg of drugs, mortality of this life-threatening GvHD was completely prevented and also other parameters like splenomegaly, erythrocyte counts and hematocrit values were strongly suppressed. Treatment of sensitized GvH-BDF1 hybrid mice in the chronic autoimmune-like model with the MNAs (30 mg/kg/day), given on days 3 to 36 by oral gavage, resulted in an improved survival rate, inhibited lymphadenopathy and splenomegaly, reduced the levels of autoantibodies and other immunoglobulins like IgE and IgG1, prevented proteinuria and the development of glomerulonephritis. Both MNA 279 and MNA 715 can inhibit ongoing aberrant immune responses in animals suffering from GvHD.
 ...
PMID:The new immunosuppressants, the malononitrilamides MNA 279 and MNA 715, inhibit various graft-vs.-host diseases (GvHD) in rodents. 951 26