3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.

Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.

ß-1,3-Glucan given orally modulates immunomyelopoietic activity and enhances the resistance of tumour-bearing mice.

ß-Glucans have been reported to be potent adjuvants in stimulating innate and adaptive immune responses. The aim of the present study was to determine the immunohematopoietic effects of Imunoglucan (HEBRON) following its oral administration to normal and Ehrlich ascites tumour (EAT)-bearing mice. Mice were treated with 250, 500 and 1000 mg/kg per day, p.o., Imunoglucan (ß-1,3-glucan extracted from Saccharomyces cerevisae) for 18 consecutive days. Treatment started 10 days prior to and ended 8 days after tumour inoculation. At 500 and 1000 mg/kg per day, Imunoglucan enhanced the life span of EAT-bearing mice and prevented myelosuppression and splenomegaly caused by the tumour by increasing the number of granulocyte-macrophage progenitors in the bone marrow and increasing colony-stimulating activity in the serum. At 500 mg/kg, Imunoglucan restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures of EAT-bearing mice and upregulated the production of interleukin (IL)-6 and IL-1α by these cells, consistent with a higher number of non-adherent cells. Moreover, 500 mg/kg Imunoglucan restored natural killer cell activity in tumour-bearing mice, consistent with the increased production of interferon (IFN)-γ observed. The results of the present study suggest that Imunoglucan given orally indirectly modulates immune activity and probably disengages tumour-induced suppression by producing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (colony-stimulating factors, IL-1α, IL-6 and IFN-γ).