The "BB" rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) and/or an insulin-dependent diabetic syndrome like that in man. All diabetic rats in this study showed marked lymphopenia in blood, lymph nodes, spleen, and thymus. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis with or without IGT or diabetes were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed marked decrease in the proportions of T+ lymphocytes in all tissues. The proportion of B (Ia+) lymphocytes was normal in blood, spleen and thymus, but increased in lymph nodes. However, in absolute terms both T and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues was that which includes helper T lymphocytes. Thus: a) generalized lymphopenia most marked for T lymphocytes has been shown, b) helper T lymphocytes show proportionally the greatest reduction, c)thymic helper T deficit suggests a thymic origin of the lymphopenia, d) lymphopenia is a possible marker for susceptibility to the syndrome.

16, 16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulmnnt viral hepatitis, murine hepatitis virus type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402±619 lU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total C02, and ALT determinations (mean ALT, 63±40 lU/liter). Treatment of infected mice with PGFu demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection.In a parallel in vitro study, dmPGE2 (10-4-10-1 M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0.In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10±5 mU/10' splenic macrophages to a maximum of 615±102 mU/106 splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.

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