Effect of Candida albicans plus histamine on prostaglandin E2 production by peripheral blood mononuclear cells from healthy women and women with recurrent candidal vaginitis.

The in vitro production of prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) in response to viable Candida albicans, histamine, and C. albicans plus histamine was examined. With PBMC from 10 healthy women, C. albicans but not histamine induced PGE2 at a low level (100 pg/ml). However, C. albicans plus histamine acted synergistically to stimulate PGE2 production (448 pg/ml). PBMC from 8 of 10 women with recurrent candidal vaginitis also produced maximal levels of PGE2 in the presence of C. albicans plus histamine. Production of tumor necrosis factor by PBMC from patients and controls was unaffected by histamine in both the presence and absence of C. albicans. However, unlike the controls, PBMC from six of the patients who were atopic and from two nonatopic patients spontaneously released PGE2 in vitro. Addition of 4 or 10 units/ml interferon-gamma inhibited spontaneous and C. albicans-induced PGE2 production by PBMC. These data reinforce the evidence that immediate hypersensitivity responses may be involved in the etiology of recurrent candidal vaginitis.

Regulation of the immune response to Candida albicans by monocytes and progesterone.

Recurrent vaginal infections caused by Candida albicans are associated with decreased cell-mediated immune responses. We report that circulating progesterone levels and variations between persons in the activity of their monocytes are two of the factors that influence the extent of lymphocyte proliferation in response to C. albicans. With the use of peripheral blood mononuclear cells from five men and four women, removal of the monocytes increased the lymphocyte response to C. albicans antigens in eight persons. The percentage increase in proliferation was inversely proportional to the proliferative response observed when the monocytes were present, suggesting that differences existed between persons in the ability of their monocytes to down regulate the response. An approximate 50% decrease in C. albicans-induced lymphocyte proliferation was observed in the presence of luteal-phase levels (25 ng/ml), as opposed to proliferative-phase levels (0.15 ng/ml) of progesterone. Monocyte removal obviated the ability of 25 ng/ml progesterone to inhibit this response, suggesting that progesterone inhibited lymphocyte proliferation through a monocyte-dependent mechanism. Thus fluctuations in a woman's monocyte activity in response to genetic, hormonal, or environmental factors may influence her ability to mount an effective cell-mediated immune response to C. albicans.

Enhancement of germ tube formation in Candida albicans by beta-endorphin.

Candida albicans is a dimorphic yeast that causes vaginal infections after its transition from a budding yeast to a germinating hyphal form. We report here that physiologic concentrations of beta-endorphin, a neuropeptide with immunomodulating activity produced during stress or physical exercise, stimulates germ tube formation in C. albicans. The percent of germination was proportional to the endorphin concentration, over the 5 x 10(-12) to 5 x 10(-10) mol/L range tested. beta-Endorphin modified by removal of the 4-carboxy-terminal amino acids and (D-Ala2)-beta-endorphin, a peptide with a protease-resistant amino terminal end, were equally effective in stimulating germination. In contrast, N-acetylated beta-endorphin did not stimulate germination. Antisera to beta-endorphin also completely blocked beta-endorphin-stimulated germ tube formation. Two clinical isolates of C. albicans were also responsive to beta-endorphin. Stimulation of germ tube formation by beta-endorphin occurred only in sera from ovulating women. Germination in sera from women using oral contraceptives, in sera from men, or in glucose beef extract broth was not influenced by beta-endorphin. Thus C. albicans may be able to recognize and respond to neuroendocrine signals in ovulating women.

Individual differences in tumour necrosis factor and interleukin-1 production induced by viable and heat-killed Candida albicans.

The in vitro production of tumour necrosis factor (TNF) and interleukin-1 (IL-1) by peripheral blood mononuclear cells from 27 healthy women in response to viable and heat-killed Candida albicans was measured. Production of both cytokines was proportional to the concentration of viable C. albicans and increased at a steady rate for at least 24 h. No relationship was observed between the levels of IL-1 and TNF produced by the mononuclear cells from any individual. Some women were high TNF producers and low IL-1 producers or vice versa. Higher levels of TNF were induced by heat-killed C. albicans than by viable organisms in 26 of the 27 subjects. In marked contrast, IL-1 was induced preferentially by viable C. albicans in 23 of the 27 women. Thus, TNF and IL-1 production induced by C. albicans appears to be non-coordinately regulated and may involve different Candida moieties.

Prostaglandin E2 enhances and gamma interferon inhibits germ tube formation in Candida albicans.

Prostaglandin E2 (PGE2), an immunosuppressive monokine that increases intracellular cyclic AMP (cAMP) levels, stimulated Candida albicans germ tube formation. Dibutyryl cAMP (dB-cAMP) and isoproterenol, other compounds that increase cAMP levels, also stimulated germination. Gamma interferon (IFN-gamma), a product of cellular immune system activation, inhibited Candida germ tube formation, even in the presence of PGE2, dB-cAMP, and isoproterenol. Thus, PGE2 and IFN-gamma as well as having opposing roles in the suppression or activation of cell-mediated immunity, are also antagonists for the yeast-to-hyphal transition of C. albicans.

Candida albicans: cellular immune system interactions during different stages of the menstrual cycle.

Candidal vaginitis most often recurs during pregnancy and in the late luteal phase just before menstruation. We examined the influence of the stage of the menstrual cycle on the cellular immune response to Candida albicans, the efficiency of C. albicans germination in sera, and the ability of products from activated lymphoid cells to inhibit germination. C. albicans germination was maximal in sera obtained during the luteal phase. During this period the cellular immune response to Candida was reduced as was the inhibition of Candida germination by products of activated peripheral blood mononuclear cells. Variations in immune response to Candida were of much lesser magnitude in women who took oral contraceptives, which suggests that it was the marked fluctuation in progesterone or estradiol levels during the menstrual cycle that influenced the changes in the immune response to C. albicans. Thus the hormonal status of women may influence the pathogenicity of C. albicans by modulation of immune system activity. These results explain the clinical observation that candidal vaginitis infections most frequently reappear before menstruation.