RESUMO
For decades, it has been known that females are more susceptible than males to multiple sclerosis (MS). It has also long been appreciated that during late pregnancy there is a decrease in MS disease activity. Interestingly, these two observations have also been made in an extensively used animal model for MS, experimental autoimmune encephalomyelitis (EAE) in SJL mice. Female mice are more susceptible to disease than male mice, and there is an improvement in disease during late pregnancy. In this review, the role of sex hormones in each of these two observations is characterized in this EAE model using castration and exogenous hormone treatment strategies. The gender difference in EAE susceptibility is due primarily to a protective effect of testosterone in male mice. The decrease in disease severity during late pregnancy appears to be due at least in part to high levels of estriol, which characterize this time period.
Assuntos
Encefalomielite Autoimune Experimental/fisiopatologia , Hormônios Esteroides Gonadais/fisiologia , Esclerose Múltipla/fisiopatologia , Animais , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
"Classic" myelin basic proteins (MBPs) are demonstrated in lymph nodes of SJL mice by western blot and RT-PCR. Interestingly, expression of these "classic" MBPs was increased during the late relapsing phase of adoptive experimental autoimmune encephalomyelitis (EAE). When splenocytes from SJL mice were separated into macrophage versus B lymphocyte-enriched populations, intact MBP isoforms were demonstrated in the macrophage-enriched population while undetectable in the B lymphocyte-enriched population. RT-PCR demonstrated "classic" MBP transcripts in splenic macrophages, as well as in a macrophage cell line (RAW). The expression of "classic" MBPs in lymphoid tissue macrophages raises the possibility that MBP-specific T cells may be exposed to autoantigen outside the central nervous system (CNS).