RESUMEN
New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.
Asunto(s)
Colitis Ulcerosa/terapia , Enfermedad de Crohn/terapia , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ensayos Clínicos como Asunto , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Defensinas/efectos adversos , Defensinas/uso terapéutico , Trasplante de Microbiota Fecal , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Integrinas/antagonistas & inhibidores , Lecitinas/uso terapéutico , Probióticos/efectos adversos , Probióticos/uso terapéutico , Ustekinumab/uso terapéuticoRESUMEN
Malaria is a mosquito-borne disease affecting millions of people mainly in Sub-Saharan Africa, Asia and some South American countries. Drug resistance to first-line antimalarial drugs (e.g. chloroquine, sulfadoxine-pyrimethamine and artemisinin) is a major constrain in malaria control. Antimicrobial peptides (AMPs) have shown promising results in controlling Plasmodium spp. parasitemia in in vitro and in vivo models of infection. Defensins are AMPs that act primarily by disrupting the integrity of cell membranes of invasive microbes. We previously showed that defensins from the tick Ixodes ricinus inhibited significantly the growth of P. falciparum in vitro, a property that was conserved during evolution. Here, we tested the activity of three I. ricinus defensins against P. chabaudi in mice. A single dose of defensin (120⯵l of 1â¯mg/ml solution) was administered intravenously to P. chabaudi-infected mice, and the parasitemia was followed for 24â¯h post-treatment. Defensin treatment inhibited significantly the replication (measured as increases in parasitemia) of P. chabaudi after 1â¯h and 12â¯h of treatment. Furthermore, defensin injection was not associated with toxicity. These results agreed with the previous report of antiplasmodial activity of tick defensins against P. falciparum in vitro and justify further studies for the use of tick defensins to control malaria.
Asunto(s)
Antimaláricos/uso terapéutico , Defensinas/uso terapéutico , Ixodes/química , Malaria/tratamiento farmacológico , Plasmodium/efectos de los fármacos , Administración Intravenosa , Animales , Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Defensinas/administración & dosificación , Defensinas/efectos adversos , Modelos Animales de Enfermedad , Femenino , Malaria/parasitología , Ratones , Ratones Endogámicos BALB C , Parasitemia/tratamiento farmacológico , Parasitemia/parasitologíaRESUMEN
Virtually all life forms express short antimicrobial cationic peptides as an important component of their innate immune defenses. They serve as endogenous antibiotics that are able to rapidly kill an unusually broad range of bacteria, fungi and viruses. Consequently, considerable efforts have been expended to exploit the therapeutic potential of these antimicrobial peptides. Within the last couple of years, it has become increasingly clear that many of these peptides, in addition to their direct antimicrobial activity, also have a wide range of functions in modulating both innate and adaptive immunity. For one class of antimicrobial peptides, such as the human defensins, their primary role may even be as immunomodulators. These properties potentially provide entirely new therapeutic approaches to anti-infective therapy.