Fetal alcohol exposure augments the blunting of tumor necrosis factor production in vitro resulting from in vivo priming with lipopolysaccharide in young adult male but not female rats.

We previously reported altered responses of thymocytes and splenocytes to mitogen stimulation in fetal alcohol-exposed (FAE) male Sprague-Dawley rats. We also reported enhanced neuroendocrine responses to stressful stimuli in these animals. The experiments we describe herein aimed at testing whether young adult FAE rats manifest a notable dysregulation in the neuroendocrine-immune response to pathogen administration. We tested the effect of in vivo priming of the animal with a low dose of endotoxin [lipopolysaccharide (LPS), 5 micrograms/kg], considered to be suboptimal from the perspective of mounting detectable levels of circulating monokines several hours after administration, upon the production of immunoreactive tumor necrosis factor (TNF-alpha) in response to a further in vitro challenge of peripheral blood mononuclear cells with 2.5 micrograms/ml of LPS 90 min after priming. We show that the response to the LPS pathogen in vitro after priming is significantly blunted (p < 0.01) in male rats exposed prenatally to alcohol, compared with control male animals. FAE female rats and FAE ovariectomized female rats do not show significant differences in the priming response, compared with control animals. We also show that there is no correspondence between plasma corticosterone levels and TNF-alpha production after priming in any of the groups tested.

Cellular immune correlates of clinical severity in oral lichen planus: preliminary association with mood states.

OBJECTIVES: We investigated cellular immune and psycho-immune dysfunctions in patients with erosive and non-erosive oral lichen planus (OLP) lesions. METHODS: Patients with erosive or non-erosive OLP were screened at the UCLA Dental Clinic. The profile of mood states (POMS) was administered. T lymphocyte subpopulations were monitored by dual fluorescence. T lymphocytes were stimulated with phytohemagglutinin (PHA) for assessment of markers of activation by flow cytometry and of interleukin (IL)-2 production by ELISA. Plasma cortisol and neopterin levels were assessed by radioimmunoassay. RESULTS: Circulating T cells that express the cluster of differentiation no. 4 (CD4+) but devoid of the CD45RA marker, and POMS score were significantly associated (r = 0.83, P < 0.05) in the patients we studied. We found a significantly higher (P < 0.05) per cent and absolute lymphocyte numbers of circulating CD4+CD45RA- cells in the OLP patients with erosive lesions, compared to OLP patients with non-erosive lesions. The ratio of CD4+ CD45RA+ over CD4+CD45RA- cells was significantly (P < 0.05) biased toward the CD4+CD45RA- subpopulation in OLP patients with erosive lesions (ratio = 0.19 +/- 0.09) compared to patients with non-erosive OLP lesions (ratio = 0.47 +/- 0.15). The expression of CD54, but not that of CD69, was significantly blunted (P < 0.05) in OLP patients following CD3+ cell stimulation. IL-2 production and plasma neopterin were normal in these patients. There was no correlation between plasma cortisol and T cell populations. CONCLUSIONS: We find fine differences in psycho-immune interactions between patients afflicted with non-erosive OLP lesions compared to those with erosive OLP lesions.

Immune surveillance of the oral cavity and lymphocyte migration: relevance for alcohol abusers.

The health of the oral cavity is threatened by a variety of microorganisms. Impaired immune surveillance of the oral environment contributes to the development of infectious processes and tumors of the mouth. Elucidation of the physiological mechanisms that determine and control oral immune surveillance is crucial to an understanding of these oral diseases. The ability of lymphocytes to migrate is critical for successful immune surveillance. the cardinal facets of lymphocyte migration are reviewed here in the context of the oral cavity. One mechanism by which alcohol acts as an important cofactor in the onset and development of oral diseases is hypothesized to be through impaired lymphocyte migration to and from peri-oral lymphoid tissue.

Immunotoxicity of cocaethylene.

This report describes the response of normal human T cells to stimulation in vitro in the presence of nano-micromolar concentrations of cocaethylene. Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear cells was generally blunted by cocaethylene, albeit to different degrees depending upon the donor tested. The formation of concanavalin A-induced blast cells was decreased by increasing concentrations of cocaethylene. The production of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene, and this outcome was more consistently observed in stimulated peripheral blood mononuclear cells, compared to unseparated whole blood preparations. An inverse dose dependence was obtained in relation to the response of blast cells to recombinant human interleukin-2 in the presence of cocaethylene. These lines of evidence, taken together with our preliminary studies aimed at testing the effect of cocaethylene on the expression of certain membrane markers of activation (i.e., interleukin-2 receptor, transferrin receptor, serine aminopeptidase IV) and the expression of the proliferating cell nuclear antigen (cyclin PCNA), suggest that cocaethylene modulates relatively early events following T cell stimulation probably related to the interleukin-2 system.