Biomedical subjects

G A Madkour

Publications and source records attributed to G A Madkour.

3 recordsLinked to original sources

PubMed2000

beta-estradiol suppresses T cell-mediated delayed-type hypersensitivity through suppression of antigen-presenting cell function and Th1 induction.

BACKGROUND: Although an immunomodulatory role for estrogens has long been demonstrated by experimental and clinical observations, the mechanism by which estrogens exert their effect on T cells has not been clearly defined. METHODS: In this study we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on the delayed-type hypersensitivity (DTH) to purified protein derivatives (PPD) and associated immune response in female mice. RESULTS: E2 treatment decreased PPD-specific DTH response, which coincided with a decrease in the leukocytes numbers in the draining lymph nodes (DLN) and spleen compared with control mice. E2 treatment also suppressed the in vitro PPD-specific proliferative response of DLN and spleen cells from PPD-primed mice. The analysis of production and gene expression of cytokines by DLN cells demonstrated that E2 treatment suppressed IL-2 and IFN-gamma production in response to PPD in vitro. In contrast, IL-4 and IL-10 gene expression by DLN cells of E2-treated mice, taken 24 h after in vivo restimulation of mice with PPD, was enhanced. Furthermore, we found that spleen APC from E2-treated mice failed to induce optimum proliferation of the PPD-primed T cells in response to PPD in vitro. The impaired APC function by E2 was not due to induction of suppressor cell activity because addition of the normal spleen APC to APC from E2-treated mice restored the proliferative response of the PPD-primed T cells in response to PPD. CONCLUSION: Our results suggest that the E2-mediated inhibition of DTH reaction is due to a combination of the down regulation of APC function and deviation of the immune response from Th1-type to Th2-type.

Animals↗

PubMed1999

Beta-estradiol-induced decrease in IL-12 and TNF-alpha expression suppresses macrophage functions in the course of Listeria monocytogenes infection in mice.

Mice treated with a contraceptive dose of beta-estradiol (E2) demonstrated changes in their macrophage (Mphi) number and functions. While E2 increased and decreased the Mphi number in PBMC and PEC respectively, it enhanced the in vitro phagocytosis of FITC-labeled beads by both cells. E2 treatment also enhanced the phagocytic function of Mphi as assessed by the in vivo carbon clearance assay. In contrast, the in vitro intracellular killing function of adherent cells in peritoneal exudate cells (PEC) against Listeria monocytogenes decreased after E2 treatment. In line with the decrease in the intracellular killing function, the E2-treated mice showed an impaired protection against L. monocytogenes infection. To clarify the mechanism of the E2-mediated suppression of the protective response against L. monocytogenes infection, we next analyzed the cytokine expression by PEC in E2-treated L. monocytogenes-infected mice. On day 5 of the infection, the expression of IL-12, TNF-alpha and IL-10 by adherent PEC from the E2-treated mice was lower than that from the control-infected mice. The decrease in the cytokine expression by adherent PEC of E2-treated mice coincided with the decrease of IFN-gamma expression, and the increase in the IL-4, IL-10 and TGF-beta expressions by non-adherent PEC. These results revealed two aspects of the effects of E2 on Mphi. Even though E2 was found to enhance Mphi phagocytosis, the anti-bacterial function was suppressed. This suppression may be mediated by the inhibition of both IL-12 and TNF-alpha which play important roles in the protective response against intracellular bacteria.

Animals↗

PubMed1997

Restraint stress-induced elevation of endogenous glucocorticoid suppresses migration of granulocytes and macrophages to an inflammatory locus.

It has been reported that restraint stress gives rise to various immunosuppressive events. In the present study, we focused our interest on an early stage of the host-defense system in which granulocytes, macrophages and natural killer (NK) cells are involved. We observed that an elevation of endogenous glucocorticoid levels in mice induced by 24 h-restraint stress (acute stress) did not significantly reduce the NK activity of the spleen cells but profoundly suppressed the migration of macrophages and granulocytes into peritoneal cavities of the mice at 24 h after an intraperitoneal injection of proteose peptone. The reduced number of the migrated granulocytes and macrophages corresponded to a down-regulated gene expression of such chemotactic factors as MCP-1/JE in the peritoneal exudate cells of the stress-loaded mice. The stress-loaded mice recovered from such a suppressive state upon treatment with the glucocorticoid antagonist, RU-486, or upon adrenalectomy, suggesting that the elevated level of endogenous glucocorticoid is responsible for these suppressive effects of acute stress.

Adrenalectomy↗