Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep

ObjectiveWe hypothesized that fetal innate immune responses to lipopolysaccharide-induced chorioamnionitis would alter postnatal systemic immune and airway responsiveness.Study DesignEwes received intraamniotic injections with saline or lipopolysaccharide at 90, 100, and 110 days of gestation. Immune status and airway responsiveness were evaluated at term and at 7 weeks of age.ResultsAt term, lymphocytes, monocytes, and neutrophils were significantly increased (respectively, 24-fold, 127-fold, and 31,000-fold) in lungs and blood monocytes became Toll-like receptor 2 responsive after lipopolysaccharide exposures. Furthermore, CD4 and CD4/CD25 lymphocytes were increased in thymus and lymph nodes. At 7 weeks, airway reactivity decreased and concentrations of CD8 cytotoxic T lymphocytes changed in the lungs and thymus relative to controls.ConclusionEarly gestational lipopolysaccharide exposure increased leukocyte responsiveness at term. Decreased airway reactivity and changes in lymphocytes at 7 weeks postnatal demonstrate persistent effects of fetal exposure to LPS

Oromucosal Administration of Interferon to Humans

The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza