RESUMO
Thirty-six out of 40 healthy volunteers responded with a markedly elevated blood interferon (IFN) content to a single oral administration of dipyridamole (a 100 mg dose): 958.0 +/- 23.5 IU/ml serum at the 24th-48th hour. A hyporeactivity state to the repeated inducer application was found within the time interval of 4th-6th day. It was established that 7/8 of the dipyridamole-induced IFN represented IFN-alpha.
Assuntos
Dipiridamol/farmacologia , Indutores de Interferon , Adulto , Feminino , Humanos , Interferons/sangue , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The kinetics of interferon (IFN) production was studied in mice after intraperitoneal (i.p.) and oral administrations of dipyridamole. The substance showed a high IFN-inducing activity when given orally at single doses ranging from 12.5 to 100 mg/kg (1/21.5-1/172 of the single LD50 value): peak titres of 2048-4096 IU/ml in the blood serum were reached at 48 hr; elevated IFN levels persisted until day 5 after administration of the inducer. Significantly lower IFN titres were found after i.p. injection.
Assuntos
Dipiridamol/farmacologia , Indutores de Interferon , Interferon Tipo I/biossíntese , Administração Oral , Animais , Dipiridamol/administração & dosagem , Feminino , Injeções Intraperitoneais , Cinética , Células L/efeitos dos fármacos , CamundongosRESUMO
2,6-Bis(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-pyrimidine (dipyridamole) induced interferon production in vitro in explanted mouse peritoneal leukocytes and to a lower degree in non-lymphoidal cell cultures of mouse (L cells primary embryo fibroblasts) and human (diploid embryo lung fibroblasts) origin. Dipyridamole induced interferon also in mice after intravenous administration. Peak interferon levels in the blood (128 IU/ml) were attained at 49 hr after injection of 0.1 mg dipyridamole per kg body weight and at 24 and 12 hr after injection of 0.6-1.8 and 16.7 mg/kg respectively. By its pH stability, thermostability and antigenic properties the interferon induced in mice, mouse peritoneal leukocytes and L cells corresponded to IFN-alpha and IFN-beta. This interferon-inducing capacity of dipyridamole may account for its broad-spectrum antiviral effect.
Assuntos
Dipiridamol/farmacologia , Indutores de Interferon , Interferons/biossíntese , Animais , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Células L/metabolismo , Leucócitos/metabolismo , CamundongosRESUMO
Immune complexes formed from Salmonella minnesota Re glycolipid (Gl) and its derivative DMSO-Gl with homologous antibodies exhibited stronger interferon (IFN)-inducing activity than the free Gl (4- to 32-fold increase and 8- to 64-fold increase respectively). This effect was found dose-dependent.
Assuntos
Complexo Antígeno-Anticorpo/fisiologia , Glicolipídeos/imunologia , Interferon Tipo I/biossíntese , Leucócitos/metabolismo , Salmonella/imunologia , Animais , Anticorpos Antibacterianos , Antígenos de Bactérias , Dimetil Sulfóxido , Glicolipídeos/farmacologia , CamundongosRESUMO
Studies in patients with autoimmune disorders strongly support a role for interferon (IFN) in the disease process. In the present study we investigated the in vivo production of alpha-IFN in lupus erythematosus patients after stimulation with dipyridamole, recently characterized as an alpha-IFN inducer in mice and humans. Levels of IFN were measured in serum samples from 22 patients with systemic lupus erythematosus (SLE) and 12 patients with discoid lupus erythematosus (DLE) before and 24 h after dipyridamole administration. IFN activity was assayed on human and bovine cells in parallel. Initial serum concentrations of alpha-IFN in SLE patients were markedly elevated. The percentage of DLE positive responders to dipyridamole induction was about twice as high as that found for SLE. Studies of factors responsible for IFN production in lupus erythematosus might result in better understanding of the relationship between DLE and SLE.
Assuntos
Dipiridamol/farmacologia , Interferon Tipo I/biossíntese , Lúpus Eritematoso Discoide/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , HumanosRESUMO
Electrodialysis of Salmonella minnesota Re glycolipid, or exposure to 0.2 M EDTA, pH 7.0, yields products capable of eliciting interferon production at concentrations 10-fold lower than that of the original glycolipid.
Assuntos
Glicolipídeos/farmacologia , Indutores de Interferon , Salmonella/fisiologia , Animais , Glicolipídeos/isolamento & purificação , Técnicas In Vitro , Leucócitos/metabolismo , Camundongos , SolubilidadeRESUMO
The in vitro explanted mouse peritoneal leukocytes were used for the optimization of the dipyridamole-induced interferon production. After 90-120 min incubation of cells with 30-100 microM dipyridamole, the production of interferon reached 6.4 X 10(4) IU/ml. It was demonstrated that the interferon production phase is preceded by the dipyridamole-dependent increase in cAMP concentration. The possibility of cAMP involvement in the mechanism of interferon production is being discussed.