thymosin and Nephritis

Immune nephritis in rats was induced by administration of nephrotoxic rabbit antiserum. The development of severe renal inflammation (proteinuria, edema, lipemia, increased erythrocyte sedimentation rate, and 30% mortality) was accompanied by hypercoagulation and inhibition of fibrinolysis. Repeated subcutaneous injections of thymoptin in a low dose of 0.1 microg/200 g (5 injections every other day) increased the severity of inflammation and prethrombotic state of the blood. Lengthening the period between injections (5 injections at 5-day intervals) was followed by a tendency toward attenuation of nephritis and correction of hypercoagulation. In healthy rats, thymoptin produced an opposite effect on hemostasis, which was manifested in moderate stimulation of fibrinolysis and hypocoagulation.

Topics: Animals; Fibrinolysis; Hemostasis; Nephritis; Rabbits; Rats; Thymosin

A single intravenous injection of anti-Thy-1 monoclonal antibody (mAb) 1-22-3 is known to cause reversible mesangial proliferative glomerulonephritis. However, mAb 1-22-3 injection followed by unilateral nephrectomy leads to progressive glomerulosclerosis and tubulointerstitial change with an irreversible course. To identify genes that play an important role in the irreversible progression of renal injury, we used microarray technology to identify differences in gene expression between these models. Rats were intravenously injected with mAb 1-22-3 1 week after unilateral nephrectomy (irreversible model) or a sham operation (reversible model), and rats were killed on days 4, 7, 14, 42, and 56 after the injection. complementary DNA probes prepared from kidney messenger RNAs were hybridized with oligonucleotide microarrays containing 4854 rat genes. The microarray identified 189 differentially expressed genes, having at least a two-fold difference in expression level between the two models, and they were classified into five clusters. One of the clusters consisted of genes whose expression was markedly upregulated in the irreversible model. This cluster included the genes encoding osteopontin, kidney injury molecule-1, and thymosin beta10. Increased expression of thymosin beta10 was localized mainly in macrophages in the fibrotic interstitium, and upregulation of thymosin beta10 expression was also observed in a unilateral ureteral obstruction model. The microarray analysis yielded information on the molecular mechanisms responsible for the difference in disease progression between the reversible and irreversible model of anti-Thy-1 nephritis. Thymosin beta10 may play an important role in the progression of kidney disease.

Topics: Animals; Cell Adhesion Molecules; Disease Models, Animal; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation; Immunohistochemistry; Isoantibodies; Kidney; Macrophages; Membrane Proteins; Multigene Family; Nephritis; Oligonucleotide Array Sequence Analysis; Osteopontin; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sialoglycoproteins; Thymosin

Topics: Amino Acid Sequence; Humans; In Vitro Techniques; Lupus Erythematosus, Systemic; Nephritis; Peptide Fragments; Rosette Formation; Thymosin

Topics: Amino Acid Sequence; Humans; In Vitro Techniques; Lupus Erythematosus, Systemic; Nephritis; T-Lymphocytes; Thymosin

Since prognosis seems to vary according to which of several possible types of disease is present, the first step is renal biopsy and histologic classification. Management options thereafter-both conventional (steroid therapy) and investigational (cytotoxic agents plus steroids, thymic hormone replacement, steroid "pulse" therapy)-are discussed in terms of recent clincal results and theoretical mechanisms of action.

Topics: Animals; Azathioprine; Cyclophosphamide; Humans; Kidney Glomerulus; Lupus Erythematosus, Systemic; Methylprednisolone; Mice; Nephritis; Prednisone; Thymosin